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The Journal of Dermatology Jun 2024Peroxisomal acyl-CoA oxidase 1 (ACOX1), is a peroxisomal enzyme that catalyzes β-oxidation of very-long-chain fatty acids (VLCFA). The gain-of-function variant...
Peroxisomal acyl-CoA oxidase 1 (ACOX1), is a peroxisomal enzyme that catalyzes β-oxidation of very-long-chain fatty acids (VLCFA). The gain-of-function variant p.Asn237Ser in ACOX1 has been shown to cause Mitchell syndrome (MITCH), a neurodegenerative disorder characterized by episodic demyelination, hearing loss, and polyneuropathy, through the overproduction of hydrogen peroxide. Only eight cases of MITCH have been reported. While all these patients experienced cutaneous abnormalities, detailed skin features and potential treatment have not been documented. Herein, we report two MITCH patients who harbored a de novo heterozygous variant p.Asn237Ser in ACOX1 and experienced progressive ichthyosiform erythroderma. Skin histopathology revealed hyperkeratosis and parakeratosis with focal hypogranulosis as well as dyskeratotic keratinocytes. Lipid accumulation in the epidermis was observed using Oil Red O staining. Both patients exhibited a remarkable response to treatment with the topical antioxidant N-acetylcysteine (NAC), with Patient 1 achieving complete recovery after 3 months of consistent treatment. This study provides the first comprehensive description of the clinicopathological characteristics and effective treatment of skin lesions in MITCH patients. The successful treatment with topical NAC suggests excessive reactive oxygen species might play a significant role in the pathogenesis of skin lesions in MITCH.
PubMed: 38923010
DOI: 10.1111/1346-8138.17346 -
Head and Neck Pathology Jun 2024Uremic stomatitis is often unfamiliar to healthcare professionals. This study presents five cases of uremic stomatitis, providing a comprehensive analysis of their... (Review)
Review
BACKGROUND
Uremic stomatitis is often unfamiliar to healthcare professionals. This study presents five cases of uremic stomatitis, providing a comprehensive analysis of their demographic distribution, clinicopathological features, and management strategies based on existing literature.
METHODS
Data were collected from centers across Brazil, Argentina, Venezuela, and Mexico. Electronic searches were conducted in five databases supplemented by manual scrutiny and gray literature.
RESULTS
The series consisted of three men and two women with a mean age of 40.2 years. Lesions mostly appeared as white plaques, particularly on the tongue (100%). The median blood urea level was 129 mg/dL. Histopathological analysis revealed epithelial changes, including acanthosis and parakeratosis, with ballooned keratinocytes in the suprabasal region. Oral lesions resolved subsequent to hemodialysis in three cases (75%). Thirty-seven studies comprising 52 cases of uremic stomatitis have been described hitherto. Most patients were male (65.4%) with a mean age of 43.6 years. Clinically, grayish-white plaques (37.3%) and ulcers/ulcerations (28.9%) were common, particularly on the tongue (30.9%). Hemodialysis was performed on 27 individuals. The resolution rate of oral lesions was 53.3%.
CONCLUSION
Earlier recognition of uremic stomatitis, possibly associated with long-term uremia, holds the potential to improve outcomes for patients with undiagnosed chronic kidney disease.
Topics: Humans; Male; Female; Adult; Uremia; Stomatitis; Middle Aged; Latin America; Renal Dialysis
PubMed: 38896178
DOI: 10.1007/s12105-024-01652-3 -
BMJ Case Reports Jun 2024
Topics: Humans; Axilla; Parakeratosis; Female; Male
PubMed: 38862187
DOI: 10.1136/bcr-2023-257394 -
Indian Journal of Dermatology 2024Pityriasis Rosea (PR) is a common, yet enigmatic, dermatological condition characterized by a distinctive clinical presentation. Despite its prevalence, the aetiology...
BACKGROUND
Pityriasis Rosea (PR) is a common, yet enigmatic, dermatological condition characterized by a distinctive clinical presentation. Despite its prevalence, the aetiology and pathogenesis of PR remain elusive.
AIMS
To study the epidemiological and clinical aspects of patients with PR. To study dermoscopic findings and carry out histopathological correlation.
METHODS
A cross-sectional study of 50 patients was conducted. A detailed clinical history was taken and an examination was done followed by a dermoscopy. Quantitative data like age and duration of disease are presented with the help of standard deviation. Qualitative risk factors, like gender, age groups, symptomatology, site of lesion, findings or cutaneous examination, dermoscopy findings, and histopathology findings, are presented with the help of frequency and percentages.
RESULTS
PR shows male preponderance and mean age of occurrence being 30.8 ± 15.7 years. Forty per cent of patients had an atypical clinical presentation. The most frequently seen dermoscopy findings were diffuse red background (58%), peripheral collarette scale (62%), and peripheral dotted vessels (50%). On histopathology, the most common findings were spongiosis (44%), parakeratosis (38%), irregular acanthosis (34%), perivascular lymphocytic infiltrate (56%), and red blood cell extravasation (36%).
LIMITATIONS
Sample size was less due to COVID. As this was a corss-sectional study follow up of patients could not be done.
CONCLUSION
While the diagnosis of PR is clinical, it is difficult in atypical cases where dermoscopy comes to the aid. It also helps identify the age of lesions, thus helping decide the treatment strategy for patients. Biopsy remains the gold standard in ruling out other differentials of PR.
PubMed: 38841213
DOI: 10.4103/ijd.ijd_1071_23 -
Frontiers in Immunology 2024Psoriasis is a chronic inflammatory disease affecting skin and joints characterized by a chronically altered immune and inflammatory response. Several factors occur from... (Review)
Review
Psoriasis is a chronic inflammatory disease affecting skin and joints characterized by a chronically altered immune and inflammatory response. Several factors occur from the onset to the development of this disease due to different types of cells spatially and temporally localized in the affected area, such as, keratinocytes, macrophages, neutrophils and T helper lymphocytes. This scenario leads to the chronic release of high levels of inflammatory mediators (, IL-17, IL-23, IL-22, TNF-α, S100 proteins, Defensins) and lastly parakeratosis and thickening of the stratum spinosum. Extracellular vesicles (EVs) are small double membraned biological nanoparticles that are secreted by all cell types and classified, based on dimension and biogenesis, into exosomes, microvesicles and apoptotic bodies. Their role as vessels for long range molecular signals renders them key elements in the pathogenesis of psoriasis, as well as innovative platforms for potential biomarker discovery and delivery of fine-tuned anti-inflammatory therapies. In this review, the role of EVs in the pathogenesis of psoriasis and the modulation of cellular microenvironment has been summarized. The biotechnological implementation of EVs for therapy and research for new biomarkers has been also discussed.
Topics: Humans; Psoriasis; Extracellular Vesicles; Biomarkers; Animals; Skin; Cellular Microenvironment
PubMed: 38827737
DOI: 10.3389/fimmu.2024.1360618 -
The Journal of Investigative Dermatology May 2024UBE2N, a Lys63-ubiquitin conjugating enzyme, plays critical roles in embryogenesis and immune system development and function. However, its roles in adult epithelial...
UBE2N, a Lys63-ubiquitin conjugating enzyme, plays critical roles in embryogenesis and immune system development and function. However, its roles in adult epithelial tissue homeostasis and pathogenesis are unclear. We generated conditional mouse models that deleted Ube2n in skin cells in a temporally and spatially controlled manner. We found that Ube2n-knockout (KO) in the adult skin keratinocytes induced a range of inflammatory skin defects characteristic of psoriatic and actinic keratosis. These included inflammation, epidermal and dermal thickening, parakeratosis, and increased immune cell infiltration, as well as signs of edema and blistering. Single cell transcriptomic analyses and RT-qPCR showed that Ube2n KO keratinocytes expressed elevated myeloid cell chemo-attractants such as Cxcl1 and Cxcl2 and decreased the homeostatic T lymphocyte chemo-attractant Ccl27a. Consistently, the infiltrating immune cells were predominantly myeloid-derived cells including neutrophils and M1-like macrophages that expressed high levels of inflammatory cytokines such as Il1β and Il24. Pharmacological blockade of the IL-1 receptor associated kinases (IRAK1/4) alleviated inflammation, epidermal and dermal thickening, and immune infiltration of the Ube2n mutant skin. Together, these findings highlight a key role of keratinocyte-UBE2N in maintenance of epidermal homeostasis and skin immunity, and identify IRAK1/4 as potential therapeutic target for inflammatory skin disorders.
PubMed: 38796140
DOI: 10.1016/j.jid.2024.04.017 -
The Journal of Dermatology May 2024Over the past few years, cases of human papillomavirus (HPV) infection in nail Bowen's disease have been reported. This disease presents diagnostic challenges due to its...
Over the past few years, cases of human papillomavirus (HPV) infection in nail Bowen's disease have been reported. This disease presents diagnostic challenges due to its similarity to nail malignant melanoma, particularly with respect to the clinical manifestation of black nail streaks. While skin biopsy is usually employed for diagnosis, it is an invasive procedure. We report the case of a 52-year-old healthy Japanese male with a pigmented streak on the nail of the fourth finger of his right hand, which had extended from the central to the lateral nail fold within 4 months. Dermoscopic examination revealed a dark-brown pigmented band with splinter microhemorrhage. Clinically, nail Bowen's disease was suspected. The lesion was excised in strips under local anesthesia. Histopathological examination revealed hyperkeratosis, parakeratosis, papillomatosis, and dyskeratotic cells with atypical nuclei irregularly arranged. Immunohistochemistry using anti-HPV L1 antibody detected HPV-positive cells in the upper epidermis and stratum corneum of the nail matrix. Mucosal high-risk HPV type 58 DNA was detected from brush cytology of the keratotic surface prior to surgery, which was confirmed in formalin-fixed, paraffin-embedded excised samples using polymerase chain reaction (PCR) and subsequent direct DNA sequencing. Our case highlights HPV type 58 as a potential causative agent of nail Bowen's disease and shows that brush cytology of the surface material prior to excision may be a useful and less invasive way for mucosal high-risk HPV detection. PCR analysis of the nail surface could serve as a supplementary diagnostic tool for nail Bowen's disease.
PubMed: 38785200
DOI: 10.1111/1346-8138.17279 -
International Journal of Dermatology May 2024
PubMed: 38757634
DOI: 10.1111/ijd.17253 -
Annales de Dermatologie Et de... Jun 2024
Topics: Humans; Male; Diagnosis, Differential; Genital Diseases, Male; Parakeratosis; Penis; Psoriasis
PubMed: 38678769
DOI: 10.1016/j.annder.2024.103268 -
The American Journal of Dermatopathology Jun 2024The aim of this study was to investigate whether the histopathological findings of psoriasis varied by the biopsied lesion location. Age, gender, age at disease onset,... (Comparative Study)
Comparative Study
The aim of this study was to investigate whether the histopathological findings of psoriasis varied by the biopsied lesion location. Age, gender, age at disease onset, lesion locations, presence or absence of a preliminary diagnosis of psoriasis, and histopathological findings of 307 patients were recorded. The sections prepared from the patients' paraffin blocks were reexamined microscopically, the severity of the observed findings was graded, and various histopathological features were recorded. The female-to-male ratio was 1.2 to 1. Family history for psoriasis was positive in 30% of patients. A clinically preliminary diagnosis of psoriasis was present in 232 patients. The most common histopathological features included hyperkeratosis, parakeratosis, Munro/Kogoj microabscesses, suprapapillary thinning-hypogranulosis, and vascular dilation-capillary proliferation. Hyperkeratosis was least common in the trunk. A linear and moderately strong correlation was found between the histopathological findings of inflammation, capillary proliferation, and suprapapillary thinning. For the first time, the clinical and demographic features of psoriasis are evaluated and the severity of the histopathological findings is compared by the biopsied lesion location in a large number of patients.
Topics: Humans; Psoriasis; Female; Male; Middle Aged; Adult; Aged; Biopsy; Young Adult; Adolescent; Child; Severity of Illness Index; Aged, 80 and over; Skin; Child, Preschool
PubMed: 38648044
DOI: 10.1097/DAD.0000000000002648