Proposal for a 6-step approach for differential diagnosis of neonatal erythroderma.

The broad differential diagnosis of neonatal erythroderma often poses a diagnostic challenge. Mortality of neonatal erythroderma is high due to complications of the erythroderma itself and the occasionally severe and life-threatening underlying disease. Early correct recognition of the underlying cause leads to better treatment and prognosis. Currently, neonatal erythroderma is approached on a case-by-case basis. The purpose of this scoping review was to develop a diagnostic approach in neonatal erythroderma. After a systematic literature search in Embase (January 1990 - May 2020, 74 cases of neonatal erythroderma were identified, and 50+ diagnoses could be extracted. Main causes were the ichthyoses (40%) and primary immunodeficiencies (35%). Congenital erythroderma was present in 64% (47/74) of the cases, predominantly with congenital ichthyosis (11/11; 100%), Netherton syndrome (12/14, 86%) and Omenn syndrome (11/23, 48%). Time until diagnosis ranged from 102 days to 116 days for cases of non-congenital erythroderma and congenital erythroderma respectively. Among the 74 identified cases a total of 17 patients (23%) died within a mean of 158 days and were related to Omenn syndrome (35%), graft-versus-host disease (67%) and Netherton syndrome (18%). Disease history and physical examination are summarized in this paper. Age of onset and a collodion membrane can help to narrow the differential diagnoses. Investigations of blood, histology, hair analysis, genetic analysis and clinical imaging are summarized and discussed. A standard blood investigation is proposed, and the need for skin biopsies with lympho-epithelial Kazal-type related Inhibitor staining is highlighted. Overall, this review shows that diagnostic procedures narrow the differential diagnosis in neonatal erythroderma. A 6-step flowchart for the diagnostic approach for neonatal erythroderma during the first month of life is proposed. The approach was made with the support of expert leaders from international multidisciplinary collaborations in the European Reference Network Skin-subthematic group Ichthyosis.

Human Papillomavirus-type distribution in anogenital lesions of prepubertal children.

BACKGROUND: In contrast to adults, only limited data are available on the human papillomavirus (HPV)-type spectrum in anogenital warts (AGW) of children. OBJECTIVE: This study aimed to evaluate the HPV-type spectrum in AGW of prepubertal children. MATERIALS & METHODS: In a retrospective German multicentre study, HPV genotyping was performed in AGW biopsies of 55 1- to 12-year-old children using HPV group-specific PCRs followed by hybridization with type-specific probes or sequence analysis. RESULTS: Human papillomavirus-DNA was found in 53 of the 55 AGW. In 58.5% (31/53) of the HPV-positive AGW, mucosal HPV types were detected. HPV6 (27/53, 50.9%) was the predominant type. 43.4% (23/53) of the lesions were induced by cutaneous HPV types (HPV2, HPV27, HPV57). Mucosal HPV types were significantly more common in children under 5 years of age than in children 5 years of age and older (22/25, 88.0% [95% CI: 70.0-95.8] vs. 9/28, 32.1% [95% CI: 17.9-50.7], P < 0.001). In contrast, cutaneous HPV types were significantly more prevalent in the 5- to 12-year age group (4/25, 16.0% [95% CI 6.4-34.7] vs. 19/28, 67.9% [95% CI 49.3-82.1], P < 0.001). CONCLUSION: Anogenital warts in 5- to 12-year-old children are frequently associated with cutaneous HPV types, possibly due to horizontal transmission. HPV typing, in addition to comprehensive clinical and psychosocial evaluation, can potentially help in the assessment of these cases.

Man against machine reloaded: performance of a market-approved convolutional neural network in classifying a broad spectrum of skin lesions in comparison with 96 dermatologists working under less artificial conditions.

BACKGROUND: Convolutional neural networks (CNNs) efficiently differentiate skin lesions by image analysis. Studies comparing a market-approved CNN in a broad range of diagnoses to dermatologists working under less artificial conditions are lacking. MATERIALS AND METHODS: One hundred cases of pigmented/non-pigmented skin cancers and benign lesions were used for a two-level reader study in 96 dermatologists (level I: dermoscopy only; level II: clinical close-up images, dermoscopy, and textual information). Additionally, dermoscopic images were classified by a CNN approved for the European market as a medical device (Moleanalyzer Pro, FotoFinder Systems, Bad Birnbach, Germany). Primary endpoints were the sensitivity and specificity of the CNN's dichotomous classification in comparison with the dermatologists' management decisions. Secondary endpoints included the dermatologists' diagnostic decisions, their performance according to their level of experience, and the CNN's area under the curve (AUC) of receiver operating characteristics (ROC). RESULTS: The CNN revealed a sensitivity, specificity, and ROC AUC with corresponding 95% confidence intervals (CI) of 95.0% (95% CI 83.5% to 98.6%), 76.7% (95% CI 64.6% to 85.6%), and 0.918 (95% CI 0.866-0.970), respectively. In level I, the dermatologists' management decisions showed a mean sensitivity and specificity of 89.0% (95% CI 87.4% to 90.6%) and 80.7% (95% CI 78.8% to 82.6%). With level II information, the sensitivity significantly improved to 94.1% (95% CI 93.1% to 95.1%; P < 0.001), while the specificity remained unchanged at 80.4% (95% CI 78.4% to 82.4%; P = 0.97). When fixing the CNN's specificity at the mean specificity of the dermatologists' management decision in level II (80.4%), the CNN's sensitivity was almost equal to that of human raters, at 95% (95% CI 83.5% to 98.6%) versus 94.1% (95% CI 93.1% to 95.1%); P = 0.1. In contrast, dermatologists were outperformed by the CNN in their level I management decisions and level I and II diagnostic decisions. More experienced dermatologists frequently surpassed the CNN's performance. CONCLUSIONS: Under less artificial conditions and in a broader spectrum of diagnoses, the CNN and most dermatologists performed on the same level. Dermatologists are trained to integrate information from a range of sources rendering comparative studies that are solely based on one single case image inadequate.

[Current indications for plasma therapy in dermatology]. / Aktuelle Indikationen der Plasmatherapie in der Dermatologie.

BACKGROUND: Plasma medicine is gaining increasing interest and provides a multitude of dermatological applications. Cold atmospheric pressure plasma (CAP) can be used in clinical applications without harming the treated tissue or in a tissue destructive manner. It consists of a complex mixture of biologically active agents, which can act synergistically on the treated material or tissue. OBJECTIVES: A summary of the current research findings regarding dermatological applications of CAP is provided. METHODS: Literature on CAP applications in dermatology has been screened and summarized. RESULTS: CAP exerts antimicrobial, tissue-stimulating, blood-flow-stimulating but also pro-apoptotic effects. By exploiting these properties, CAP is successfully applied for disinfection and treatment of chronic ulcerations. Furthermore, positive effects of CAP have been shown for the treatment of tumors, actinic keratosis, scars, ichthyosis, atopic eczema as well as for alleviation of pain and itch. CONCLUSIONS: While the use of CAP for disinfection and wound treatment has already moved into clinical practice, further applications such as cancer treatment are still exploratory.

[Cold atmospheric pressure plasma for the treatment of acute and chronic wounds]. / Kaltes Atmosphärendruckplasma zur Behandlung akuter und chronischer Wunden.

BACKGROUND: Besides acute wounds (through trauma or surgical interventions), chronic wounds comprise a relatively large and heterogeneous group of diseases. These include leg ulcers with venous disease greatly prevailing arterial disease, diabetic foot syndrome, and pressure ulcers. Due to a considerable treatment resistance against such therapies, new and effective, additive treatment options especially for chronic wounds are needed. Wound treatment with cold atmospheric plasma (CAP) constitutes such an innovative option. OBJECTIVES: Current research regarding the efficacy of cold plasma for healing of acute and chronic wounds is summarized. MATERIALS AND METHODS: The literature on CAP applications in wound healing has been screened and reviewed. RESULTS: With CAP, several effects that promote wound healing can be simultaneously applied in one application. On the one hand, CAP exerts a strong and broad antimicrobial activity against biofilm. On the other hand, the plasma cocktail, which consists of reactive nitrogen and oxygen species, UV, and charged particles (electrical current), mediates tissue-stimulating, blood flow-promoting, and anti-inflammatory effects. Marked germ reduction on wounds and accelerated wound healing have already been convincingly demonstrated in controlled clinical studies. CONCLUSIONS: The comprehensive CAP study landscape with structured case report summaries and randomized case-control studies allows the conclusion that CAP is safe, effective, and easy to handle for wound treatment. The utilization of CAP in addition to standard wound treatments is starting to enter routine clinical practice.

[Increased revenues from secondary diagnoses : A comparison from dermatology, ophthalmology, and infectious diseases]. / Mehrerlöse durch Nebendiagnosen : Ein Vergleich von Dermatologie, Ophthalmologie und Infektiologie.

BACKGROUND: Hospital revenues generated by diagnosis-related groups (DRGs) are in part dependent on the coding of secondary diagnoses. Therefore, more and more hospitals trust specialized coders with this task, thereby relieving doctors from time-consuming administrative burdens and establishing a highly professionalized coding environment. However, it is vastly unknown if the revenues generated by the coders do indeed exceed their incurred costs. METHODS: Coding data from the departments of dermatology, ophthalmology, and infectious diseases from Rostock University Hospital from 2007-2016 were analyzed for the effects of secondary diagnoses on the resulting DRG, i. e., hospital charges. RESULTS: Ophthalmological case were highly resistant to the addition of secondary diagnoses. In contrast, adding secondary diagnoses to cases from infectious diseases resulted in 15% higher revenues. Although dermatological and infectious cases share the same sensitivity to secondary diagnoses, higher revenues could only rarely be realized in dermatology, probably owing to a younger, less multimorbid patient population. CONCLUSION: Except for ophthalmology, trusting specialized coders with clinical coding generates additional revenues through the coding of secondary diagnoses which exceed the costs for employing these coders.

A novel mutation in the XPA gene results in two truncated protein variants and leads to a severe XP/neurological symptoms phenotype.

BACKGROUND: The nucleotide excision repair (NER) pathway repairs UV-induced DNA lesions in an accurate fashion and prevents UV-irradiated areas of the skin from tumour formation. The XPA protein plays a major role in DNA damage demarcation as well as stabilization of other NER factors and was found to be defective in xeroderma pigmentosum (XP) complementation group A patients. OBJECTIVE: Characterization of four new XP-A patients. METHODS: Genomic and cDNA sequencing, post-UV cell survival of living cells, host-cell reactivation of patients' fibroblasts and Western blotting. RESULTS: One of the four investigated patients shows a novel mutation leading to two different truncated protein variants. Three patients contain the already described p.R228X mutation. All patient cell lines exhibit a strong UVC sensitivity and reduced NER capability. In most of the cases stable protein expression was detected. CONCLUSION: We discovered four new XP-A patients and a novel XPA mutation resulting in two diverse patient alleles.

Melanoma thickness: the role of patients' characteristics, risk indicators and patterns of diagnosis.

BACKGROUND: Factors associated with early vs. late diagnosis of cutaneous melanoma remain poorly understood. OBJECTIVE: To identify factors with a significant impact on melanoma thickness. METHODS: Patients with previous melanoma (n = 347, median age at diagnosis: 56.5 years, 44.7% female, 55.3% male) were recruited for this monocentre, non-randomized, observational study between April 2012 and March 2013. All patients were assessed by means of a structured interview and systematic clinical and dermoscopic full-body examination. Melanoma thickness in association with patients' characteristics, risk indicators and patterns of diagnosis was submitted to statistical analyses. RESULTS: Univariate analyses revealed associations between a statistically significant lower Breslow thickness and participation in specialized dermoscopic screening programs, personal history of more than one previous melanoma, diagnostic examination with a dermatoscope, diagnostic examination by board certified dermatologist, high number of common and/or atypical nevi, younger age at time of diagnosis, higher level of education, or superficial spreading or lentigo maligna melanoma subtype (all P ≤ 0.01). In a multivariate regression analysis only three of these criteria: (i) participation in specialized screening programs (P < 0.0001); (ii) melanoma subtype (P < 0.0001); and (iii) diagnostic examination with a dermatoscope (P = 0.040) and one interaction term ('younger age' x 'female sex', P < 0.0001) showed an independent influence on a significantly lower melanoma thickness. CONCLUSIONS: The screening of patients in specialized surveillance programs resulted in melanoma detection at significantly earlier stages. The use of dermoscopy, SSM or LMM histotype and younger age in connection with female sex were also characteristics that were independently associated with significantly thinner melanomas in multivariate analyses.

Alleviation of chronic venous leg ulcers with a hand-held dielectric barrier discharge plasma generator (PlasmaDerm(®) VU-2010): results of a monocentric, two-armed, open, prospective, randomized and controlled trial (NCT01415622).

BACKGROUND: Cold atmospheric plasma (CAP, i.e. ionized air) is an innovating promising tool in reducing bacteria. OBJECTIVE: We conducted the first clinical trial with the novel PlasmaDerm® VU-2010 device to assess safety and, as secondary endpoints, efficacy and applicability of 45 s/cm(2) cold atmospheric plasma as add-on therapy against chronic venous leg ulcers. METHODS: From April 2011 to April 2012, 14 patients were randomized to receive standardized modern wound care (n = 7) or plasma in addition to standard care (n = 7) 3× per week for 8 weeks. The ulcer size was determined weekly (Visitrak® , photodocumentation). Bacterial load (bacterial swabs, contact agar plates) and pain during and between treatments (visual analogue scales) were assessed. Patients and doctors rated the applicability of plasma (questionnaires). RESULTS: The plasma treatment was safe with 2 SAEs and 77 AEs approximately equally distributed among both groups (P = 0.77 and P = 1.0, Fisher's exact test). Two AEs probably related to plasma. Plasma treatment resulted in a significant reduction in lesional bacterial load (P = 0.04, Wilcoxon signed-rank test). A more than 50% ulcer size reduction was noted in 5/7 and 4/7 patients in the standard and plasma groups, respectively, and a greater size reduction occurred in the plasma group (plasma -5.3 cm(2) , standard: -3.4 cm(2) ) (non-significant, P = 0.42, log-rank test). The only ulcer that closed after 7 weeks received plasma. Patients in the plasma group quoted less pain compared to the control group. The plasma applicability was not rated inferior to standard wound care (P = 0.94, Wilcoxon-Mann-Whitney test). Physicians would recommend (P = 0.06, Wilcoxon-Mann-Whitney test) or repeat (P = 0.08, Wilcoxon-Mann-Whitney test) plasma treatment by trend. CONCLUSION: Cold atmospheric plasma displays favourable antibacterial effects. We demonstrated that plasma treatment with the PlasmaDerm® VU-2010 device is safe and effective in patients with chronic venous leg ulcers. Thus, larger controlled trials and the development of devices with larger application surfaces are warranted.

[Palmoplantar dermatoses: when should genes be considered?]. / Hautveränderungen an Händen und Füßen: Wann muss man an die Gene denken?

BACKGROUND: Palmoplantar dermatoses are common. They can be both functionally debilitating and markedly stigmatize the patient because they are so visible. Dermatoses on the hands and feet often go along with palmoplantar hyperkeratosis. Such palmoplantar keratoses (PPK) can be classified into acquired (non-hereditary) and hereditary (monogenetic) PPK. OBJECTIVES: A considerable proportion of PPK develop on the grounds of gene defects. As these diseases constitute a heterogeneous group of quite uncommon single entities, the treating physician must know when to entertain the diagnosis of a hereditary PPK and which causative genes should be considered. METHODS: We summarize the common causes of acquired and hereditary PPK based on a review of the latest literature. RESULTS: The most common causes of acquired PPK are inflammatory dermatoses like psoriasis, lichen planus, or hand and feet eczema. Also irritative-toxic (arsenic poisoning, polycyclic aromatic hydrocarbons) and infectious causes of PPK (human papilloma viruses, syphilis, scabies, tuberculosis, mycoses) are not uncommon. Genetically caused PPK may occur isolated, within syndromes or as a paraneoplastic marker. The clinical/histological classification discerns diffuse, focal, or punctuate forms of PPK with and without epidermolysis. A new classification based on the causative gene defect is starting to replace the traditional clinical classification. CONCLUSIONS: Knowledge about the large, but heterogeneous group of hereditary PPK is important to adequately counsel and treat patients and their families.

Diagnosis and treatment of malignant eyelid tumors.

BACKGROUND: Malignant tumors of the eyelid are much less frequent than benign eyelid alterations. These are frequently incidental findings without symptoms which are often overlooked or misinterpreted by patients. OBJECTIVE: This article gives an overview of clinical aspects, diagnostics and treatment of the five most common malignant eyelid tumors and exemplarily explains the essential principles of evidence-based treatment of malignant eyelid tumors. METHODS: This narrative review was prepared based on a selective literature search. The depiction of the treatment of eyelid tumors is supported by illustrations of clinical cases. RESULTS: The medical history and inspection provide initial indications of malignancy. Every eyelid change suspected of being malignant should be examined histologically to confirm a diagnosis. By far the most common malignant eyelid tumor in Europe is basal cell carcinoma, which metastasizes only in exceptional cases. Squamous cell carcinomas, sebaceous adenocarcinomas, melanomas and Merkel cell carcinomas occur much less frequently. In these cases, potential metastasis in particular must be considered when making the diagnosis and staging has to be initiated. Surgical excision into healthy tissue with tumor-free margins is the gold standard for malignant eyelid tumors. Non-surgical adjuvant or neoadjuvant forms of evidence-based treatment can be initiated based on the individual case to minimize the risk of recurrence and metastasis. CONCLUSION: It is essential to recognize eyelid changes at an early stage, to classify them correctly and to initiate the appropriate treatment. The interaction between the general condition and the personal needs of a patient as well as state of the art medicine are the keys to a good personalized treatment.

[X-linked recessive ichthyosis (XRI), cerebellar ataxia and neuropsychiatric symptoms]. / X-chromosomal-rezessive Ichthyose (XRI) mit zerebellärer Ataxie, Angsterkrankung und Depression.

X-Linked ichthyosis (XRI) is a keratinisation disorder caused by a mutation of the steroid sulfatase gene. An association with mental retardation and epilepsy has been reported earlier. Here, we report on a patient suffering from cerebellar symptoms such as yes/yes head tremor, scanning dysarthria, pronounced dysmetria and intention tremor, without any abnormalities of the cerebellum in MRI, in addition to XRI proven by molecular genetics. Furthermore, the patient suffered from anxiety disorder, depression, and a male pattern baldness. One of the patient' s brothers and a nephew showed a similar clinical presentation. Because of the fact that several members of the patient's family suffered from similar symptoms, we consider a syndromic link between XRI and cerebellar disorder to be possible.

[Diagnosis and treatment of malignant eyelid tumors]. / Diagnose und Therapie der malignen Lidtumoren.

BACKGROUND: Malignant tumors of the eyelid are much less frequent than benign eyelid alterations. These are frequently incidental findings without symptoms which are often overlooked or misinterpreted by patients. OBJECTIVE: This article gives an overview of clinical aspects, diagnostics and treatment of the five most common malignant eyelid tumors and exemplarily explains the essential principles of evidence-based treatment of malignant eyelid tumors. METHODS: This narrative review was prepared based on a selective literature search. The depiction of the treatment of eyelid tumors is supported by illustrations of clinical cases. RESULTS: The medical history and inspection provide initial indications of malignancy. Every eyelid change suspected of being malignant should be examined histologically to confirm a diagnosis. By far the most common malignant eyelid tumor in Europe is basal cell carcinoma, which metastasizes only in exceptional cases. Squamous cell carcinomas, sebaceous adenocarcinomas, melanomas and Merkel cell carcinomas occur much less frequently. In these cases, potential metastasis in particular must be considered when making the diagnosis and staging has to be initiated. Surgical excision into healthy tissue with tumor-free margins is the gold standard for malignant eyelid tumors. Non-surgical adjuvant or neoadjuvant forms of evidence-based treatment can be initiated based on the individual case to minimize the risk of recurrence and metastasis. CONCLUSION: It is essential to recognize eyelid changes at an early stage, to classify them correctly and to initiate the appropriate treatment. The interaction between the general condition and the personal needs of a patient as well as state of the art medicine are the keys to a good personalized treatment.

Expanding the keratin mutation database: novel and recurrent mutations and genotype-phenotype correlations in 28 patients with epidermolytic ichthyosis.

BACKGROUND: Epidermolytic ichthyosis (EI) is a hereditary keratinization disorder caused by mutations in the keratin 1 (KRT1) or keratin 10 (KRT10) genes. In most cases of severe EI, heterozygous single point mutations are found at the highly conserved helix boundary motifs of KRT1 and KRT10 that play a critical role in filament formation. The presence of palmoplantar keratoderma suggests KRT1 mutations, whereas KRT10 mutations in most instances give rise to the nonpalmoplantar variants. OBJECTIVES: To identify the underlying mutations in patients with EI and to correlate genotype and phenotype. METHODS: Mutation analysis was performed in 28 patients with EI by direct sequencing of KRT1 and KRT10 genes. RESULTS: We identified 14 different mutations, of which four have not been published previously. CONCLUSIONS: Identification of novel mutations and genotype-phenotype correlations in EI allows improved understanding of disease pathogenesis as well as better patient management.

CEDNIK syndrome results from loss-of-function mutations in SNAP29.

BACKGROUND: CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis and keratoderma) syndrome is a rare genodermatosis which was shown 5 years ago in one family to be associated with a loss-of-function mutation in SNAP29, encoding a member of the SNARE family of proteins. Decrease in SNAP29 expression was found to result in abnormal lamellar granule maturation leading to aberrant epidermal differentiation and ichthyosis. OBJECTIVES: To delineate the molecular consequences of disease-causing mutations in SNAP29. METHODS: We used direct sequencing, in vitro mutagenesis and three-dimensional organotypic cell cultures. RESULTS: We identified a novel homozygous insertion in SNAP29 (c.486insA) in two sibs presenting with ichthyosis and dysgenesis of the corpus callosum. In vitro transfection experiments indicated that this mutation results in SNAP29 loss-of-function. Further substantiating this notion, we could replicate histological features typical for CEDNIK syndrome in three-dimensional primary human keratinocyte organotypic cell cultures downregulated for SNAP29. CONCLUSIONS: The identification of a second mutation in SNAP29 in the present study definitely establishes a causal relationship between defective function of SNAP29 and the pleiotropic manifestations of CEDNIK syndrome. Our present and previous data position SNAP29 as an essential component of the epidermal differentiation machinery.

Antiproliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repair.

While investigating the novel anticancer drug ecteinascidin 743 (Et743), a natural marine product isolated from the Caribbean sea squirt, we discovered a new cell-killing mechanism mediated by DNA nucleotide excision repair (NER). A cancer cell line selected for resistance to Et743 had chromosome alterations in a region that included the gene implicated in the hereditary disease xeroderma pigmentosum (XPG, also known as Ercc5). Complementation with wild-type XPG restored the drug sensitivity. Xeroderma pigmentosum cells deficient in the NER genes XPG, XPA, XPD or XPF were resistant to Et743, and sensitivity was restored by complementation with wild-type genes. Moreover, studies of cells deficient in XPC or in the genes implicated in Cockayne syndrome (CSA and CSB) indicated that the drug sensitivity is specifically dependent on the transcription-coupled pathway of NER. We found that Et743 interacts with the transcription-coupled NER machinery to induce lethal DNA strand breaks.

[Xeroderma pigmentosum (XP) : A genetic disease sheds light on UV-induced skin cancer]. / Xeroderma pigmentosum : Genetische Modellerkrankung bringt Licht ins Dunkel von UV-induziertem Hautkrebs.

The recessively inherited nucleotide excision repair (NER) defect syndrome xeroderma pigmentosum (XP) serves as a model disease for UV-induced skin cancer. XP is characterized by sun-sensitivity, freckling, and poikilodermic skin changes in sun-exposed areas, and a more than 1000-fold increased risk of skin cancer including melanoma as well as basal and squamous cell carcinomas. Seven XP complementation groups (XP-A to XP-G) are known to date representing the defective genes in XP patients. An additional "variant" form (XPV) which is clinically indistinguishable from the complementation groups exhibits defective translesional synthesis. An enhanced understanding of skin cancer development in general can help to identify individuals at an increased risk who should take special precautions, for example to avoid occupational exposures. The position of skin cancer induced by UV-light as an occupational disease in the ordinance on industrial diseases (BKV) is currently a topic of research and discussion in Germany.

[Disease management guidelines in dermatology: implementation, potentials and limitations exemplified by the guidelines for the management of hand eczema]. / Leitlinien in der Dermatologie : Umsetzung, Möglichkeiten und Grenzen am Beispiel der Leitlinie Management von Handekzemen.

In Germany, the "Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften" (AWMF; consortium of scientific medical societies) constitutes the umbrella organisation to conceive, evaluate, and release guidelines. There are 3 stages of development (S1-S3) according to the evidence level and the process of consensus finding. Currently, 59 dermatologic guidelines have been published under the auspices of the Deutsche Dermatologische Gesellschaft (German Dermatological Society). The guideline for the management of hand dermatitis (AWMF-Register-No: 013/053) is an instructive recent example. This guideline clearly demonstrates the benefits of guidelines, i.e. standardized definition of heterogeneous diseases and disease severity as well as standardized therapy algorithms. This is especially important in diseases difficult-to-treat like chronic hand dermatitis. The effective implementation of guidelines with early incorporation of new therapies, for example alitretinoin in the therapy of hand dermatitis, can considerably improve the quality of life of patients.

Papular exanthem discloses acute myeloid leukaemia: interphase fluorescence in situ hybridization revealed deletion of p53 and gain at 8q22/8q24/Tel8q without trisomy 8.

We describe a 79-year-old patient who presented with fatigue, weight loss, pancytopenia and a papular exanthem. Previous attempts to taking bone-marrow biopsies had resulted in a 'dry tap', with no material collected, suggesting idiopathic myelofibrosis. Histological examination of skin biopsies showed dermal infiltration of monocytoid cells, resulting in a diagnosis of acute myeloid leukaemia (French-American-British M5 morphology) with leukaemia cutis (LC). Numerous abnormalities of chromosome 8 (trisomy or tetrasomy) have been identified in association with LC. We performed fluorescent in situ analysis on cutaneous tissue using directly labelled probes for various gene loci often involved in patients with AML; these tests showed deletion of p53 and excluded trisomy 8. However, application of probes for AML/ETO, MYC and telomere 8q revealed a gain at 8q22/8q24/8q telomere in a significant number of infiltrating cells. We hypothesize that a partial gain at 8q rather than trisomy of the whole chromosome 8 exhibits an association with LC in AML.