TY - JOUR A1 - Hamm, Henning A1 - Höger, Peter H T1 - Skin Tumors in Childhood JF - Deutsches Ärzteblatt International N2 - Background: Dermatologists, paediatricians, and general practitioners are often consulted by worried parents for the evaluation of a cutaneous tumor. Methods: Selective literature review. Results: Only 1-2% of skin tumors excised in children turn out to be malignant when examined histologically. Warning signs of malignancy include rapid growth, firm consistency, diameter exceeding 3 cm, ulceration, a non-movable mass, and presence in the neonatal period. The more common malignant skin tumors in adults-basal cell carcinoma, cutaneous squamous cell carcinoma, and melanoma-are very rare in childhood. Congenital melanocytic nevi and sebaceous nevi bear a lower malignant potential than previously believed; nevertheless, their excision is often indicated. A Spitz nevus can mimic a melanoma both clinically and histologically. Some benign skin tumors of childhood tend to regress spontaneously within a few years but may cause complications at particular locations and when multiple. For infantile hemangiomas requiring systemic treatment because of imminent obstruction or ulceration, propranolol seems to have a far more favorable risk-benefit ratio than corticosteroids. Conclusion: Physicians need specialized knowledge in order to decide whether a skin tumor in a child should be excised, non-surgically treated, or further evaluated, or whether it can be safely left untreated because of the likelihood of spontaneous remission. KW - congenital melanocytic nevi KW - mastocytosis KW - diagnosis KW - melanoma KW - children KW - lumps Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142402 VL - 108 IS - 20 ER - TY - JOUR A1 - Rak, Katrin A1 - Hamm, Henning A1 - Kerstan, Andreas A1 - Kolb-Mäurer, Annette A1 - Goebeler, Matthias T1 - Severe and prolonged liver damage in pityriasis rubra pilaris treated with acitretin: a case report JF - SN Comprehensive Clinical Medicine N2 - Acitretin is a systemic retinoid that is used in dermatology for treatment of various inflammatory and especially hyperkeratotic diseases. Elevation of liver enzymes may occur occasionally but normally resolves spontaneously, at the latest after termination of acitretin. However, it can very rarely develop into a life-threatening adverse event including drug-induced liver injury (DILI). A 45-year-old man with classical pityriasis rubra pilaris, a frequently severe, inflammatory skin disease, was started on acitretin. After a seemingly harmless elevation of transaminases, a few weeks after initiation of acitretin, the patient experienced a dramatic course of liver injury with hepatic jaundice though acitretin was stopped immediately. Eventually, laboratory values recovered upon high-dose oral prednisolone therapy. Prescribing physicians should keep in mind that acitretin might induce severe liver injury. Even after termination of acitretin laboratory values should be monitored for a while in order to recognize symptomless but harmful drug-induced liver injury in time. KW - acitretin KW - pityriasis rubra pilaris KW - drug-induced liver injury (DILI) KW - adverse event Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-323982 VL - 4 IS - 1 ER - TY - JOUR A1 - Williams, Tatjana A1 - Machann, Wolfram A1 - Kühler, Leif A1 - Hamm, Henning A1 - Müller-Höcker, Josef A1 - Zimmer, Michael A1 - Ertl, Georg A1 - Ritter, Oliver A1 - Beer, Meinrad A1 - Schönberger, Jost T1 - Novel desmoplakin mutation: juvenile biventricular cardiomyopathy with left ventricular non-compaction and acantholytic palmoplantar keratoderma JF - Clinical Research in Cardiology N2 - Two sons of a consanguineous marriage developed biventricular cardiomyopathy. One boy died of severe heart failure at the age of 6 years, the other was transplanted because of severe heart failure at the age of 10 years. In addition, focal palmoplantar keratoderma and woolly hair were apparent in both boys. As similar phenotypes have been described in Naxos disease and Carvajal syndrome, respectively, the genes for plakoglobin (JUP) and desmoplakin (DSP) were screened for mutations using direct genomic sequencing. A novel homozygous 2 bp deletion was identified in an alternatively spliced region of DSP. The deletion 5208_5209delAG led to a frameshift downstream of amino acid 1,736 with a premature truncation of the predominant cardiac isoform DSP-1. This novel homozygous truncating mutation in the isoform-1 specific region of the DSP C-terminus caused Carvajal syndrome comprising severe early-onset heart failure with features of non-compaction cardiomyopathy, woolly hair and an acantholytic form of palmoplantar keratoderma in our patient. Congenital hair abnormality and manifestation of the cutaneous phenotype in toddler age can help to identify children at risk for cardiac death. KW - Desmoplakin KW - Juvenile biventricular cardiomyopathy KW - Palmoplantar keratoderma Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141198 VL - 100 IS - 12 ER - TY - JOUR A1 - Thomas, Anna C. A1 - Zeng, Zhiqiang A1 - Rivière, Jean-Baptiste A1 - O'Shaughnessy, Ryan A1 - Al-Olabi, Lara A1 - St.-Onge, Judith A1 - Atherton, David J. A1 - Aubert, Hélène A1 - Bagazgoitia, Lorea A1 - Barbarot, Sébastien A1 - Bourrat, Emmanuelle A1 - Chiaverini, Christine A1 - Chong, W. Kling A1 - Duffourd, Yannis A1 - Glover, Mary A1 - Groesser, Leopold A1 - Hadj-Rabia, Smail A1 - Hamm, Henning A1 - Happle, Rudolf A1 - Mushtaq, Imran A1 - Lacour, Jean-Philippe A1 - Waelchli, Regula A1 - Wobser, Marion A1 - Vabres, Pierre A1 - Patton, E. Elizabeth A1 - Kinsler, Veronica A. T1 - Mosaic activating mutations in GNA11 and GNAQ are associated with phakomatosis pigmentovascularis and extensive dermal melanocytosis JF - Journal of Investigative Dermatology N2 - Common birthmarks can be an indicator of underlying genetic disease but are often overlooked. Mongolian blue spots (dermal melanocytosis) are usually localized and transient, but they can be extensive, permanent, and associated with extracutaneous abnormalities. Co-occurrence with vascular birthmarks defines a subtype of phakomatosis pigmentovascularis, a group of syndromes associated with neurovascular, ophthalmological, overgrowth, and malignant complications. Here, we discover that extensive dermal melanocytosis and phakomatosis pigmentovascularis are associated with activating mutations in GNA11 and GNAQ, genes that encode Ga subunits of heterotrimeric G proteins. The mutations were detected at very low levels in affected tissues but were undetectable in the blood, indicating that these conditions are postzygotic mosaic disorders. In vitro expression of mutant GNA11\(^R183C\) and GNA11\(^Q209L\) in human cell lines demonstrated activation of the downstream p38 MAPK signaling pathway and the p38, JNK, and ERK pathways, respectively. Transgenic mosaic zebrafish models expressing mutant GNA11\(^R183C\) under promoter mitfa developed extensive dermal melanocytosis recapitulating the human phenotype. Phakomatosis pigmentovascularis and extensive dermal melanocytosis are therefore diagnoses in the group of mosaic heterotrimeric G-protein disorders, joining McCune-Albright and Sturge-Weber syndromes. These findings will allow accurate clinical and molecular diagnosis of this subset of common birthmarks, thereby identifying infants at risk for serious complications, and provide novel therapeutic opportunities. KW - uveal melanoma KW - G Protein KW - dermal melanocytosis KW - Sturge-Weber syndrom KW - cesioflammea KW - germline KW - phakomatosis pigmentovascularis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189689 VL - 136 IS - 4 ER - TY - JOUR A1 - Grundmeier, Natalie A1 - Hamm, Henning A1 - Weissbrich, Benedikt A1 - Lang, Sabrina Christine A1 - Bröcker, Eva-Bettina A1 - Kerstan, Andreas T1 - High-risk human papillomavirus infection in Bowen’s disease of the nail unit: report of three cases and review of the literature JF - Dermatology N2 - Background: Bowen’s disease (BD) of the nail unit is associated with human papillomavirus (HPV) infection. Objective: This study aimed to investigate the frequency of high-risk HPV infection, gender, age and digital distribution in this condition. Methods: Biopsy specimens of 3 consecutive cases with periungual BD were investigated for the presence of HPV DNA by in situ hybridization and by polymerase chain reaction (PCR). Furthermore, 74 cases of ungual BD conducted with HPV genotyping as reported in the literature were reviewed. Results: PCR of biopsy specimens revealed in 2 cases infection with HPV-16 and in 1 case with HPV-73. Additionally, in 1 HPV-16-positive case HPV-31/33 was detected by in situ hybridization. In line, review of the literature demonstrated a clear association of HPV-positive BD with high-risk HPV types. Interestingly, age at diagnosis was significantly lower in women. Whereas in both genders the second to fourth fingers on both hands were commonly diseased, only in men the thumbs were also prominently affected. Conclusions: Infection with high-risk HPV types is common in BD of the nail unit suggesting the aetiological cause. Therefore, patients and partners should be closely followed up for digital and genital HPV-associated lesions. KW - Nail unit KW - Human papillomavirus KW - Bowen’s disease, periungual Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196638 SN - 1018-8665 SN - 1421-9832 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 223 IS - 4 SP - 293 EP - 300 ER - TY - JOUR A1 - Nothhaft, Matthias A1 - Klepper, Joerg A1 - Kneitz, Hermann A1 - Meyer, Thomas A1 - Hamm, Henning A1 - Morbach, Henner T1 - Hemorrhagic bullous Henoch-Schönlein Purpura: case report and review of the literature JF - Frontiers in Pediatrics N2 - Henoch-Schönlein Purpura (HSP) or IgA vasculitis is the most common systemic vasculitis of childhood and may affect skin, joints, gastrointestinal tract, and kidneys. Skin manifestations of HSP are characteristic and include a non-thrombocytopenic palpable purpura of the lower extremities and buttocks. Rarely, HSP may initially present as or evolve into hemorrhagic vesicles and bullae. We present an otherwise healthy 5-year-old boy with an acute papulovesicular rash of both legs and intermittent abdominal pain. After a few days the skin lesions rapidly evolved into palpable purpura and hemorrhagic bullous lesions of variable size and severe hemorrhagic HSP was suspected. A histological examination of a skin biopsy showed signs of a small vessel leukocytoclastic vasculitis limited to the upper dermis and direct immunofluorescence analysis revealed IgA deposits in vessel walls, compatible with HSP. To further characterize the clinical picture and treatment options of bullous HSP we performed an extensive literature research and identified 41 additional pediatric patients with bullous HSP. Two thirds of the reported patients were treated with systemic corticosteroids, however, up to 25% of the reported patients developed skin sequelae such as hyperpigmentation and/or scarring. The early use of systemic corticosteroids has been discussed controversially and suggested in some case series to be beneficial by reducing the extent of lesions and minimizing sequelae of disease. Our patient was treated with systemic corticosteroids tapered over 5 weeks. Fading of inflammation resulted in healing of most erosions, however, a deep necrosis developing from a large blister at the dorsum of the right foot persisted so that autologous skin transplantation was performed. Re-examination 11 months after disease onset showed complete clinical remission with re-epithelialization but also scarring of some affected areas. KW - henoch-schönlein purpura KW - vasculitis KW - hemorrhagic KW - bullae KW - children Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201435 VL - 6 ER - TY - JOUR A1 - Ballin, Nadja A1 - Hotz, Alrun A1 - Bourrat, Emmanuelle A1 - Küsel, Julia A1 - Oji, Vinzenz A1 - Bouadjar, Bakar A1 - Brognoli, Davide A1 - Hickman, Geoffroy A1 - Heinz, Lisa A1 - Vabres, Pierre A1 - Marrakchi, Slaheddine A1 - Leclerc‐Mercier, Stéphanie A1 - Irvine, Alan A1 - Tadini, Gianluca A1 - Hamm, Henning A1 - Has, Cristina A1 - Blume‐Peytavi, Ulrike A1 - Mitter, Diana A1 - Reitenbach, Marina A1 - Hausser, Ingrid A1 - Zimmer, Andreas D. A1 - Alter, Svenja A1 - Fischer, Judith T1 - Genetical, clinical, and functional analysis of a large international cohort of patients with autosomal recessive congenital ichthyosis due to mutations in NIPAL4 JF - Human Mutation N2 - Autosomal recessive congenital ichthyosis (ARCI) belongs to a heterogeneous group of disorders of keratinization. To date, 10 genes have been identified to be causative for ARCI. NIPAL4 (Nipa‐Like Domain‐Containing 4) is the second most commonly mutated gene in ARCI. In this study, we present a large cohort of 101 families affected with ARCI carrying mutations in NIPAL4. We identified 16 novel mutations and increase the total number of pathogenic mutations in NIPAL4 to 34. Ultrastructural analysis of biopsies from six patients showed morphological abnormalities consistent with an ARCI EM type III. One patient with a homozygous splice site mutation, which leads to a loss of NIPAL4 mRNA, showed additional ultrastructural aberrations together with a more severe clinical phenotype. Our study gives insights into the frequency of mutations, a potential hot spot for mutations, and genotype–phenotype correlations. KW - ARCI KW - ARCI EM type III KW - collodion baby KW - ichthyosis KW - NIPAL4 Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212747 VL - 40 IS - 12 ER - TY - JOUR A1 - Almanzar, Giovanni A1 - Klein, Matthias A1 - Schmalzing, Marc A1 - Hilligardt, Deborah A1 - El Hajj, Nady A1 - Kneitz, Hermann A1 - Wild, Vanessa A1 - Rosenwald, Andreas A1 - Benoit, Sandrine A1 - Hamm, Henning A1 - Tony, Hans-Peter A1 - Haaf, Thomas A1 - Goebeler, Matthias A1 - Prelog, Martina T1 - Disease Manifestation and Inflammatory Activity as Modulators of Th17/Treg Balance and RORC/FoxP3 Methylation in Systemic Sclerosis JF - International Archives of Allergy and Immunology N2 - Background: There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. Methods: The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors. Results: There was a concurrent accumulation of circulating peripheral IL-17-producing CCR6+ Th cells and FoxP3+ Tregs in patients with dcSSc. At the transcriptional level, Th17- and Treg-associated transcription factors were elevated in SSc. A strong association with high circulating Th17 and Tregs was seen with early, active, and severe disease presentation. However, a diminished suppressive function on autologous lymphocytes was found in SSc-derived Tregs. Significant relative hypermethylation was seen at the gene level for RORC1 and RORC2 in SSc, particularly in patients with high inflammatory activity. Conclusions: Besides the high transcriptional activity of T cells, attributed to Treg or Th17 phenotype, in active SSc disease, Tregs may be insufficient to produce high amounts of IL-10 or to control proliferative activity of effector T cells in SSc. Our results suggest a high plasticity of Tregs strongly associated with the Th17 phenotype. Future directions may focus on enhancing Treg functions and stabilization of the Treg phenotype. KW - methylation KW - systemic sclerosis KW - suppression KW - Tregs KW - Th17 Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196577 SN - 1018-2438 SN - 1423-0097 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 171 IS - 2 ER - TY - JOUR A1 - Schäfer, Kristina A1 - Bauer, Boris A1 - Donhauser, Julian A1 - Kerstan, Andreas A1 - Hamm, Henning T1 - Becker Naevus Syndrome of the Lower Body: A New Case and Review of the Literature JF - Acta Dermato-Venereologica N2 - Becker naevus syndrome is a rare epidermal naevus syndrome defined by the co-occurrence of a Becker naevus with various cutaneous, muscular and skeletal anomalies. In the majority of cases, abnormalities exclusively consist of ipsilateral hypoplasia of the breast, areola and/or nipple in addition to the naevus. Here, we report on a 42-year-old woman with an extensive Becker naevus reaching from the left buttock to the left calf verified on histological examination. In addition, there was marked hypoplasia of the fatty tissue of the left thigh confirmed by magnetic resonance imaging in contrast to hyperplasia of the fatty tissue of the left gluteal area. Underlying muscles and bones were not affected. There was no difference in leg lengths. In addition, we review and discuss the features of Becker naevus syndrome with emphasis on 10 reported cases with involvement of the lower body. KW - lower body KW - Becker naevus KW - Becker naevus syndrome KW - hypoplasia of fatty tissue Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171057 VL - 97 IS - 4 ER -