Summary
Background
Cutaneous mosaicism is an area of dermatology in which there has been an explosion of knowledge within the current decade. This has led to fundamental changes in the understanding ...of the conditions in this field, and to an ongoing paradigm shift in the approach to management of mosaic skin disorders.
Objectives
To lay out the general principles of mosaicism as they are currently understood, summarize the known cutaneous mosaic abnormalities of the skin with associated phenotypic and genotypic information, review the latest trials on targeted therapies and propose guidelines for the general approach to a patient with suspected mosaicism.
Methods
This was a consensus expert review as part of the European Reference Network project (ERN‐Skin).
Conclusions
This study provides clinicians with a practical approach to the patient with suspected mosaicism, redefines mosaicism for the modern genetic era, and proposes a new classification system based on genetic mechanism.
What's already known about this topic?
Cutaneous mosaicism is a complex field of dermatology that encompasses most birthmarks, and many rare syndromes.
Some cutaneous patterns are known to be seen in mosaicism.
Very few treatment options are available for most mosaic abnormalities of the skin.
Recent high‐sensitivity genetic techniques have led to an explosion of knowledge about genotype and phenotype in the literature.
What does this study add?
Expert consensus from the European Reference Network project.
Review of knowledge of confirmed mosaic abnormalities of the skin, including cutaneous phenotype, extracutaneous associated features and genotype.
Proposed new classification of mosaic abnormalities of the skin by genetic mechanism and therefore inheritance potential.
Practical tips on correct sample collection and genetic investigation.
Review of trials of targeted therapies.
Guidelines for a practical clinical approach to the patient with suspected mosaicism.
Plain language summary available online
Skin conditions among 20th century politicians and world leaders Kluger, N.; Perciaccante, A.; Charlier, P. ...
Journal of the European Academy of Dermatology and Venereology,
December 2021, 2021-12-00, 20211201, 2021-12, Letnik:
35, Številka:
12
Journal Article
A review of cutaneous mosaicism Kinsler, V.A.; Boccara, O.; Fraitag, S. ...
British journal of dermatology (1951),
March 2020, 2020-03-00, 20200301, Letnik:
182, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Summary
Cutaneous mosaicism is a term used for a group of disorders in which a person has two or more genetically different populations of cells existing side by side within the skin. It is an area ...of dermatology in which there has been an explosion of knowledge within the current decade. This has led to fundamental changes in the understanding of the conditions in this field, and to an ongoing shift in the approach to treating mosaic skin disorders.
In this expert review, as part of the European Reference Network project (ERN‐Skin), we lay out the general principles of mosaicism as they are currently understood, summarise the known cutaneous mosaic abnormalities of the skin – including signs and symptoms and genetic information – and we review the latest trials of treatments. We also propose guidelines for the general approach to patients thought to have mosaicism.
This is a summary of the study: Mosaic abnormalities of the skin: review and guidelines from the European Reference Network for rare skin diseases
Linked Article: Kinsler et al. Br J Dermatol 2020; 182:552–563
Summary
Background
Epidermolysis bullosa simplex generalized severe (EBS‐gen sev) is a genetic disorder caused by mutation in the KRT5 or KRT14 genes. Although it is usually considered a mechanical ...disease, recent data argue for additional inflammatory mechanisms.
Objectives
To assess the inflammation in the skin of patients with EBS‐gen sev.
Methods
A first immunohistochemical retrospective study was performed on frozen skin samples from 17 patients with EBS‐gen sev. A second multicentre prospective study was conducted on 10 patients with severe EBS‐gen sev. Blister fluid and epidermis were processed for immunochemical analysis and quantitative real‐time polymerase chain reaction. Cytokine expression was analysed in blister fluid and compared with that in controls.
Results
Histological analysis showed a constant dermal perivascular CD4+ lymphocyte infiltrate in skin biopsies of both blister (n = 17) and rubbed skin (n = 5), an epidermal infiltration of neutrophils and eosinophils in 70% of cases, and increased immunostaining for CXCL9 and CXCL10 in blistering skin. High levels of T helper 17 cytokines were detected in lesional skin. Three adult patients with EBS‐gen sev were treated with apremilast, with a dramatic improvement of skin blistering and good tolerance.
Conclusions
Our study demonstrates the importance of inflammation in patients with EBS‐gen sev and underlines the key role for T helper 17 cells in its pathogenesis. In addition, this study provides promising new therapeutic approaches for this disabling disorder.
What's already known about this topic?
Epidermolysis bullosa simplex generalized severe (EBS‐gen sev) is a rare disabling skin disorder related to skin fragility.
What does this study add?
We showed the presence of an immune infiltrate characterized by a T helper (Th)17 phenotype in the skin of patients with EBS‐gen sev.
There was a marked improvement of the skin condition in patients with EBS after treatment with apremilast, an anti‐Th17 molecule.
What is the translational message?
Our results demonstrate the importance of inflammation in EBS‐gen sev and underline the key role of Th17 activation.
Anti‐Th17 molecules such as apremilast provide a promising new therapeutic approach for this disabling disorder.
Linked Comment: Mellerio. Br J Dermatol 2019; 180:258–260.
Plain language summary available online
Respond to this article
A twenty-three month old female presented with abnormal pigmentation since birth. She had a past history of mediastinal non-Hodgkin's lymphoma diagnosed at the age of 9 months and treated with ...surgery and chemotherapy. Family history revealed that her grandfathers were brothers, and both died of colon cancer in their fifth decade. Parents were both fit and well in their early thirties.
Background
Postzygotic mutations in FGFR2 have been identified in mosaic forms of acne, keratinocytic epidermal nevi, nevoid acanthosis nigricans / rounded and velvety epidermal nevus and in two ...fetuses with papillomatous pedunculated sebaceous nevus (PPSN).
Objectives
To determine the clinical and genetic characteristics of children with cerebriform, papillomatous and pedunculated variants of sebaceous nevi.
Methods
Infants diagnosed with sebaceous nevi characterized by a cerebriform, papillomatous and/or pedunculated morphology over a 10‐year period (2010–2019) at three paediatric dermatology centres in Switzerland and France were included in this case series. Clinical and histological characteristics were assessed. Next‐generation sequencing was used to assess for FGFR2 mutations.
Results
All nevi were located on the head, with a rounded or linear shape and a typical cerebriform, sometimes papillomatous and pedunculated, surface. No associated extracutaneous anomalies were found. Nevi harboured postzygotic mutations in the transmembrane domain of FGFR2 in 6/8 children (75%), either the known specific p.(Cys382Arg) mutation in 5 cases, or a novel mutation, p.(Val395Asp), in one.
Conclusions
We found an exquisite genotype–phenotype correlation in these rare nevi, with specific postzygotic mutations in the transmembrane domain of FGFR2. As not all lesions were truly papillomatous and pedunculated, the term cerebriform sebaceous nevus (CSN) appears more suitable than PPSN to describe this entity. The cerebriform pattern of CSN is reminiscent of cutis gyrata, as seen in Beare–Stevenson syndrome, which is caused by closely related germline FGFR2 mutations. While clinically impressive, CSN seem to carry a good prognosis and a low risk for extracutaneous associations.
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