Persistent Cutaneous Lesions of Darier Disease and Second-Hit Somatic Variants in ATP2A2 Gene.

Importance: Darier disease (DD) is a rare genetic skin disorder caused by heterozygous variants in the ATP2A2 gene. Clinical manifestations include recurrent hyperkeratotic papules and plaques that occur mainly in seborrheic areas. Although some of the lesions wax and wane in response to environmental factors, others are severe and respond poorly to therapy.

Biological treatment for bullous pemphigoid.

Background: Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease. Topical or systemic corticosteroids are often used as the first-line treatment. However, long-term corticosteroid use may lead to significant side effects.

Clinical features in adults with acquired cutis laxa: a retrospective review.

Acquired cutis laxa (ACL) is a very rare dermatological condition with numerous proposed aetiologies. Herein, we report on 10 adult patients with ACL, three of which were found to have genetic mutations suggesting a genetic predisposition for the development of ACL following exposure to an environmental insult. Four patients were presumed to develop ACL in association with medication exposure.

Inflammatory linear verrucous epidermal nevus (ILVEN) encompasses a spectrum of inflammatory mosaic disorders.

Background: Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare skin disease characterized by pruritic erythematous scaly plaques distributed along the lines of Blaschko. Two cases of ILVEN with CARD14 mutations and one case with a GJA1 mutation have been previously reported.

Objective: To elucidate the genetic cause of a cohort of patients diagnosed based on clinical and histopathological evaluation with ILVEN.

Erratum: Cutaneous and hepatic vascular lesions due to a recurrent somatic mutation reveal a pathway for vascular malformation.

[This corrects the article DOI: 10.1016/j.xhgg.

Pigmented demodicidosis - an under-recognized cause of facial hyperpigmentation.

Background: There is a paucity of data regarding demodicidosis-associated facial hyperpigmentation.

Objective: To delineate the clinical, dermoscopic, and histopathologic features of demodicidosis-associated facial hyperpigmentation.

Methods: Clinical and diagnostic data were collected from the medical files of patients who were referred to our outpatient dermatology clinic in 2006-2019 for evaluation of facial hyperpigmentation and were diagnosed with demodicidosis.

Cutaneous and hepatic vascular lesions due to a recurrent somatic mutation reveal a pathway for vascular malformation.

The term "cavernous hemangioma" has been used to describe vascular anomalies with histology featuring dilated vascular spaces, vessel walls consisting mainly of fibrous stromal bands lined by a layer of flattened endothelial cells, and an irregular outer rim of interrupted smooth muscle cells. Hepatic hemangiomas (HHs) and cutaneous venous malformations (VMs) share this histologic pattern, and we examined lesions in both tissues to identify genetic drivers. Paired whole-exome sequencing (WES) of lesional tissue and normal liver in HH subjects revealed a recurrent c.

Treatment of Bullous Pemphigoid in People Aged 80 Years and Older: A Systematic Review of the Literature.

Background: Bullous pemphigoid commonly affects older adults and has a detrimental effect on both quality of life and longevity. Systemic corticosteroids, the mainstay of therapy, may cause significant adverse effects, especially in older patients. Therefore, safer therapeutic options are being sought.

Stage-dependent Increase in Expression of miR-155 and Ki-67 and Number of Tumour-associated Inflammatory Cells in Folliculotropic Mycosis Fungoides.

Recent studies suggest that folliculotropic mycosis fungoides (FMF), the most common variant of mycosis fungoides (MF), presents with 2 distinct clinicopathological stages: early indolent stage and more aggressive advanced/tumour stage. To further characterize these stages, miR-155 expression was studied with qRT-PCR and found to be significantly higher in biopsies of tumour-stage FMF compared with early-stage FMF and inflammatory dermatoses. There was no statistically significant difference in miR-155 expression between early-stage FMF and early-stage MF, nor between tumour-stage FMF and tumour-stage MF.

Clues to primary vismodegib resistance lie in histology and genetics.

Basal cell carcinoma (BCC) is the most common human malignant neoplasm. However, there are multiple BCC subtypes that share clinical features while demanding different management. We present a case of a woman with hundreds of BCCs throughout her body that were resistant to vismodegib and without other features of basal cell nevus syndrome.

Post-zygotic ACTB mutations underlie congenital smooth muscle hamartomas.

Background: Congenital smooth muscle hamartomas (CSMHs) are benign lesions that share clinical and histopathological features with Becker nevus, a mosaic disorder associated with post-zygotic ACTB mutations. Given the clinical and histopathological overlap between CSMH and Becker nevus, we hypothesized that post-zygotic mutations in ACTB may underlie CSMH.

Methods: Direct sequencing of ACTB gene in affected and unaffected tissue isolated from one case of hemihypertrichosis and hemihypertrophy corresponding to giant segmental CSMH and hemihypertrophy.

Mutations in KRT10 in epidermolytic acanthoma.

Background: Epidermolytic acanthoma (EA) is a rare acquired lesion demonstrating a characteristic histopathological pattern of epidermal degeneration referred to as epidermolytic hyperkeratosis (EHK). On histopathological analysis, EA appears nearly identical to inherited EHK-associated dermatoses such as epidermolytic ichthyosis and ichthyosis bullosa of Siemens. While it has been speculated that EA is caused by mutations in KRT10, KRT1, or KRT2 found in these inherited dermatoses, none have yet been identified.

Second-Hit Somatic Mutations in Mevalonate Pathway Genes Underlie Porokeratosis.

Familial and sporadic porokeratosis are associated with germline heterozygous mutations in mevalonate pathway genes. Kubo et al. show that each skin lesion of disseminated superficial actinic porokeratosis originates from a postnatal keratinocyte clone with a different second-hit genetic event in the wild-type allele of the corresponding gene.

Recessive Mutations in AP1B1 Cause Ichthyosis, Deafness, and Photophobia.

We describe unrelated individuals with ichthyosis, failure to thrive, thrombocytopenia, photophobia, and progressive hearing loss. Each have bi-allelic mutations in AP1B1, the gene encoding the β subunit of heterotetrameric adaptor protein 1 (AP-1) complexes, which mediate endomembrane polarization, sorting, and transport. In affected keratinocytes the AP-1 β subunit is lost, and the γ subunit is greatly reduced, demonstrating destabilization of the AP-1 complex.

Phenotypic expansion of POFUT1 loss of function mutations in a disorder featuring segmental dyspigmentation with eczematous and folliculo-centric lesions.

Appearance of mosaic disorders in thin Blaschko lines suggests that somatic mutations in keratinocyte precursors underlie their pathogenesis. Germline heterozygous mutations in POFUT1 gene cause Dowling-Degos disease (DDD), a skin disease that features flexural reticulated hyperpigmentation and follicular-based lesions. POFUT1 mosaicism has not been described to date.

Topical cholesterol/lovastatin for the treatment of porokeratosis: A pathogenesis-directed therapy.

Background: Porokeratosis is associated with mevalonate pathway gene mutations. Therapeutic options are few and often limited in efficacy. We hypothesized that topical therapy that aims to replenish cholesterol, an essential mevalonate pathway end-product, and block the accumulation of mevalonate pathway toxic metabolites could alleviate porokeratosis.

Review of genodermatoses with characteristic histopathology and potential diagnostic delay.

Advances in human genetics have enabled discovery of new genes for inherited skin diseases and cutaneous malformations as well as refined categorization of genodermatoses. Careful phenotyping has been central to genetic discoveries, and it provides critical clues for clinical diagnoses, particularly when the skin disorder is not congenital. This article will review several lesser-known genodermatoses that often present after infancy with recognizable histopathologic features.

Second-Hit, Postzygotic PMVK and MVD Mutations in Linear Porokeratosis.

Importance: Linear porokeratosis features linear and whorled configurations of keratotic papules and plaques, with coronoid lamellae present on histologic examination. Because linear porokeratosis manifests in the lines of Blaschko representing the dorsoventral migration patterns of keratinocyte precursors, it has been suggested that postzygotic somatic mutation underlies the disease. However, no genetic evidence has supported this hypothesis to date.

Association of bullous pemphigoid with malignancy: A systematic review and meta-analysis.

Background: Studies evaluating whether malignancy rate is increased in patients with bullous pemphigoid (BP) have reached conflicting results.

Objective: We sought to determine whether BP is associated with malignancy.

Method: Medline, EMBASE, the Cochrane library, and reference lists of included studies were searched for comparative studies that evaluated the relationship between BP and malignancy.