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
To investigate bone involvement in a large cohort of systemic mastocytosis (SM) patients, and evaluate the efficacy of bisphosphonate therapy.
From 2000 to 2004, 75 patients with SM according to WHO ...criteria underwent skeletal x-rays and bone mineral density (BMD) assessment. Sequential BMD assessments were performed in nine patients treated with bisphosphonate (mean follow-up 65 months).
37 patients (49%) had bone involvement according to both x-rays and BMD evaluations: osteoporosis (23 patients, 31%, mean lumbar spine T score: -3 SD), with vertebral fracture (13 patients, 17%), axial skeleton osteosclerosis (six patients, 8%), mixed patterns (three patients), osteopenia with pre-existing fractures (four patients) and focal osteolytic lesion (one patient). Blood count abnormalities were associated with osteosclerosis (p=0.005). In nine patients with osteoporosis and bisphosphonate therapy, mean lumbar spine BMD increased from 0.83 to 0.92 g/cm(2) (+11.1%; ie, +2.05% per year) without recurrence of vertebral fracture.
Half of adult patients with SM have bone involvement. Osteoporosis is the most prevalent bone manifestation in SM (31%). Bisphosphonate therapy seems efficient to improve lumbar spine BMD during SM-related osteoporosis. Spine x-ray and BMD should be performed in all SM patients to detect those who may benefit from anti-osteoporotic therapy.
Summary
Paediatric mastocytosis was previously considered to be a benign and spontaneously regressing disease. However, this evolution is impossible to predict. To clarify the characteristics and ...course of paediatric mastocytosis, we performed a literature review of 1747 cases published between 1950 and April 2014. Lesions occurred before the age of 2 years in 90% of cases, and presented as urticaria pigmentosa (75% of cases), mastocytoma (20%) or diffuse cutaneous mastocytosis (5%). The male‐to‐female ratio was 1·4. KIT D816V mutation was detected in 34% of 215 tested patients. Clinical regression (complete or partial) occurred in 67% of cases and stabilization in 27%. However, the outcome was fatal in 2·9% of patients.
What's already known about this topic?
The clinical and genetic features and outcomes of mastocytosis differ for the adult and paediatric forms.
Since paediatric mastocytosis was linked to mutations in c‐Kit in 2010, it has been considered a clonal disease.
In 1963, Caplan reported that spontaneous regression occurs in the majority of cases of paediatric mastocytosis, and no predictive factors have been identified.
What does this study add?
This extensive review points out that the outcome in some paediatric cases is fatal, that KIT mutations are rarely studied and that predictive factors are still unknown.
We suggest that long‐term follow‐up of children is necessary and that prospective studies are warranted to evaluate the prognostic value of sequencing KIT.
Skin manifestations among GATA2‐deficient patients Polat, A.; Dinulescu, M.; Fraitag, S. ...
British journal of dermatology (1951),
March 2018, 2018-03-00, 20180301, 2018-03, Letnik:
178, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Summary
GATA2 mutations have been identified in various diseases, such as MonoMAC syndrome, Emberger syndrome, familial myelodysplastic syndrome, acute myeloid leukaemia and dendritic cell, monocyte, ...B‐cell and natural killer‐cell deficiency. These syndromes present a wide range of clinical features, dominated by severe infections and haematological disorders such as myelodysplastic syndrome. Up to 70% of patients with GATA2 mutations have dermatological features, mainly genital or extragenital warts, panniculitis or erythema nodosum and lymphoedema. We report three patients presenting with common dermatological and haematological features leading to the diagnosis of GATA2 deficiency, but also with skin manifestations that have not been previously described: gingival hypertrophy, macroglossitis and glossitis and granulomatous lupoid facial lesions. Dermatologists can encounter patients with GATA2 mutations and should recognize this disorder.
What's already known about this topic?
GATA2 deficiency is a recently described genetic disorder featuring mainly haematological manifestations and infectious conditions.
Dermatological features include warts and other infectious disorders, lymphoedema and panniculitis/erythema nodosum.
What does this study add?
We report three cases of patients with GATA2 mutations with dermatological features not previously described.
Linked Comment: Nanda. Br J Dermatol 2018; 178:593–594.
Background
Paediatric cutaneous granuloma with primary immunodeficiency (PID) is a rare condition. The physiopathology is unclear, and treatment is challenging. We report on 17 paediatric cases and ...review the literature.
Objectives
To make dermatologists and dermatopathologists aware of the diagnostic value of skin granulomas in paediatric PID.
Methods
We collected data on 17 patients with cutaneous granulomas and PID registered with us and also reviewed 33 cases from the literature.
Results
Cutaneous granuloma was the presenting feature of the PID in 15 of the 50 collated cases. The lesions presented as red‐brownish nodules and infiltrated ulcerative plaques, predominantly on the face and limbs. Scleroderma‐like infiltration on a single limb was observed in 10% of the cases. The associated PID was ataxia‐telangiectasia (52%), combined immunodeficiency (24%), cartilage‐hair hypoplasia (6%) and other subtypes (18%). The granulomas were mostly sarcoidal, tuberculoid, palisaded or undefined subtypes. In some patients, several different histopathologic granulomatous patterns were found in the same biopsy. Some granulomas were associated with the presence of a vaccine strain of rubella virus.
Conclusion
Cutaneous granulomas associated with a PID have a variable clinical presentation. A PID can be suspected when crusty, brownish lesions are found on the face or limbs. The concomitant presence of several histological subtypes in a single patient is suggestive of a PID.
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
Granulomas may develop as a response to a local antigenic trigger, leading to the activation of macrophages and T-lymphocytes. Primary immunodeficiency (PID) is associated with the development of ...extensive cutaneous granulomas, whose aetiology remains unknown. We performed high-throughput sequencing of the transcriptome of cutaneous granuloma lesions on two consecutive index cases, and RT-PCR in a third consecutive patient. The RA27/3 vaccine strain of rubella virus—the core component of a universally used paediatric vaccine—was present in the cutaneous granuloma of these three consecutive PID patients. Controls included the healthy skin of two patients, non-granulomatous cutaneous lesions of patients with immunodeficiency, and skin biopsy samples of healthy individuals, and were negative. Expression of viral antigens was confirmed by immunofluorescence. Persistence of the rubella vaccine virus was also demonstrated in granuloma lesions sampled 4-5 years earlier. The persistence of the rubella virus vaccine strain in all three consecutive cutaneous granuloma patients with PID strongly suggests a causal relationship between rubella virus and granuloma in this setting.
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