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PloS One 2020Hereditary nasal parakeratosis (HNPK) is an inherited disorder described in Labrador Retrievers and Greyhounds. It has been associated with breed-specific variants in...
Hereditary nasal parakeratosis (HNPK) is an inherited disorder described in Labrador Retrievers and Greyhounds. It has been associated with breed-specific variants in the SUV39H2 gene encoding a histone 3 methyltransferase involved in epigenetic silencing. Formalin-fixed biopsies of the nasal planum of Labrador Retrievers were screened by immunofluorescence microscopy for the presence and distribution of epidermal proliferation and differentiation markers. Gene expression of these markers was further analysed using RNA sequencing (RNA-seq) and ultrastructural epidermal differences were investigated by electron microscopy. Differentiation of the nasal planum in the basal and suprabasal epidermal layers of HNPK-affected dogs (n = 6) was similar compared to control dogs (n = 6). In the upper epidermal layers, clear modifications were noticed. Loricrin protein was absent in HNPK-affected nasal planum sections in contrast to sections of the same location of control dogs. However, loricrin was present in the epidermis of paw pads and abdominal skin from HNPK dogs and healthy control dogs. The patterns of keratins K1, K10 and K14, were not markedly altered in the nasal planum of HNPK-affected dogs while the expression of the terminal differentiation marker involucrin appeared less regular. Based on RNA-seq, LOR and IVL expression levels were significantly decreased, while KRT1, KRT10 and KRT14 levels were up-regulated (log2fold-changes of 2.67, 3.19 and 1.71, respectively) in HNPK-affected nasal planum (n = 3) compared to control dogs (n = 3). Electron microscopical analysis revealed structural alterations in keratinocytes and stratum corneum, and disrupted keratinocyte adhesions and distended intercellular spaces in lesional samples (n = 3) compared to a sample of a healthy control dog (n = 1). Our findings demonstrate aberrant keratinocyte terminal differentiation of the nasal planum of HNPK-affected Labrador Retrievers and provide insights into biological consequences of this inactive SUV39H2 gene variant.
Topics: Animals; Dogs; Female; Male; Antigens, Differentiation; Dog Diseases; Genetic Diseases, Inborn; Keratinocytes; Nose Diseases; Parakeratosis
PubMed: 32119674
DOI: 10.1371/journal.pone.0225901 -
Case Reports in Gastroenterology 2020Medication-induced esophagitis is a well-known but relatively rare clinical diagnosis, most common in patients with preexisting esophageal dysmotility, obstruction, or...
Medication-induced esophagitis is a well-known but relatively rare clinical diagnosis, most common in patients with preexisting esophageal dysmotility, obstruction, or altered anatomy. Esophagitis dissecans superficialis (EDS) is a rare endoscopic finding characterized by sloughing of large fragments of the esophageal mucosal lining. The causes of EDS include prior trauma, heavy smoking history, ingestion of alcoholic and hot beverages, and immunosuppression. We present a unique case of EDS secondary to ferrous sulfate-induced pill esophagitis. The patient was a 94-year-old male who presented with dysphagia to solids, odynophagia, and weight loss. Esophagogastroduodenoscopy (EGD) revealed EDS. Biopsies demonstrated vacuolar degeneration at the midlevel of the epithelium with overlying hyperkeratosis and parakeratosis, with noted black/brown pigment present at the level of the split in the epithelium. The patient was started on a liquid diet with no oral administration of pills. EGD was repeated and showed a significant improvement in esophageal mucosa and resolution of strictures. Although medication-induced esophagitis is not classically associated with EDS, specific circumstances that are associated with pill esophagitis may lead to progression to EDS. In the case of our patient, prolonged contact of ferrous sulfate to the esophageal mucosa is thought be a result of an enlarged left atrium and pulmonary arteries secondary to longstanding coronary artery disease and an enlarged left bronchus secondary to chronic obstructive pulmonary disease and right pneumonectomy. These anatomical changes likely led to an extended duration of contact and are believed to have led to erosion of the superficial esophageal mucosa, eventually progressing to EDS.
PubMed: 32399000
DOI: 10.1159/000506935 -
Medicine and Pharmacy Reports Jul 2020Sarcoidosis is a multisystem granulomatous disease of unknown etiology and cutaneous involvement is the second most frequent manifestation in systemic sarcoidosis.The...
BACKGROUND AND AIMS
Sarcoidosis is a multisystem granulomatous disease of unknown etiology and cutaneous involvement is the second most frequent manifestation in systemic sarcoidosis.The aim of the present study is to evaluate the clinical and pathological spectrum of cutaneous sarcoidosis and compare the same with literature available.
METHODS
The present retrospective study was conducted from January 2010-March 2015 and fifteen cases diagnosed as cutaneous sarcoidosis on biopsy were reviewed. The histological spectrum of cutaneous sarcoidosis was evaluated.
RESULTS
The mean age at diagnosis was 46 years. Nine (60%) cases out of 15 were females. Most common cutaneous lesions were nodules (46.6%) followed by papules (40%). Classically, lymphocyte-poor, non-caseating epithelioid cell granulomas, was the most common histologic finding. Inclusion bodies were seen in 20% cases with occasional presence of fibrinoid necrosis (13.3%). Peri-adnexal granuloma, seen in one case, raised the possibility of tuberculoid leprosy. Foreign body was seen in one case supporting the opinion that sarcoidosis and granulomatous foreign body reaction are not mutually exclusive. Epidermal changes including atrophy, loss of rete pegs, acanthosis, papillomatosis, hyperkeratosis, parakeratosis and basal cell vacuolation were seen in 46.6% cases. Reticulin was positive in all the cases while special stains for acid fast bacilli and fungi were negative.
CONCLUSION
The clinical presentation of cutaneous sarcoidosis may be variable. Presence of naked, reticulin-rich granulomas is the most characteristic histopathological finding. Correlation of clinical history with histologic examination is essential to exclude other granulomatous diseases including leprosy, syphilis, other infectious granulomatous diseases and foreign body reaction.
PubMed: 32832888
DOI: 10.15386/mpr-1384 -
Clinical Proteomics 2020(PV) is a chronic autoimmune inflammatory disease with epidermal hyperkeratosis and parakeratosis.
BACKGROUND
(PV) is a chronic autoimmune inflammatory disease with epidermal hyperkeratosis and parakeratosis.
METHODS
The study was to elucidate the pathogenesis of PV by quantitative proteomic analysis of skin lesion biopsies of PV and healthy tissues with tandem mass tags (TMTs) coupled with liquid chromatography-mass spectrometry (LC-MS)/MS.
RESULTS
A total of 4562 differentially expressed proteins (DEPs) between PV lesional tissues (n = 11) and healthy tissues (n = 11) were identified, of which 299 were upregulated and 206 were downregulated using |fold change| > 1.3 as the cutoff threshold. The Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the DEPs were mainly enriched in the activation of immune cells (drug metabolism pathway, NOD-like pathway, and IL-17 pathway), cell proliferation (ribosomal pathway, DNA replication pathway, and base replication pathway), metabolism-related pathways (fatty acid biosynthesis and metabolism, PPAR pathway, glycerophospholipid metabolism, and cortisol synthesis and breakdown), and glandular secretion (saliva secretion, gastric acid secretion, and pancreatic fluid secretion). Thirteen DEPs that were relatively highly expressed in the drug metabolism pathway were validated with parallel reaction monitoring (PRM), of which MPO, TYMP, IMPDH2, GSTM4, and ALDH3A1 were highly expressed in PV, whereas CES1, MAOB, MGST1, and GSTT1 were less expressed in PV.
CONCLUSIONS
These findings confirmed that these proteins participate in the drug metabolism-other enzyme pathways and play crucial roles in the activation and proliferation of immune cells in the pathogenesis of PV.
PubMed: 32817748
DOI: 10.1186/s12014-020-09293-8 -
Clinical, Cosmetic and Investigational... 2023Granular parakeratosis (GP) is a unique keratotic disorder that often affects the intertriginous areas. GP usually presents as erythematous or brownish hyperkeratotic...
Granular parakeratosis (GP) is a unique keratotic disorder that often affects the intertriginous areas. GP usually presents as erythematous or brownish hyperkeratotic papules or plaques and can be further classified into five types. GP of the eccrine ostium is a rare subtype; its pathological defects are mainly localized to the stratum corneum of the eccrine ostia. Due to its rarity, there is usually a delay in diagnosing GP, and these patients are often misdiagnosed with other dermatological conditions. In this report, we present the case of a 64-year-old Thai female who presented with recurrent pruritic erythematous rashes on her neck since approximately 40 years. She was previously diagnosed with eczema or folliculitis. Histopathological examination confirmed a final diagnosis of GP of the eccrine ostium. She was advised to avoid excessive heat and keep her intertriginous areas dry. Her condition improved significantly during the follow-up visit.
PubMed: 37469551
DOI: 10.2147/CCID.S421152 -
Journal of the European Academy of... Dec 2021The treatment of keratinocyte cancers (KC) strictly depends on their differentiation and invasiveness. Non-invasive diagnostic techniques can support the diagnosis in...
BACKGROUND
The treatment of keratinocyte cancers (KC) strictly depends on their differentiation and invasiveness. Non-invasive diagnostic techniques can support the diagnosis in real time, avoiding unnecessary biopsies. This study aimed to preliminarily define main imaging criteria and histological correlations of actinic keratosis (AK), Bowen's disease (BD) and squamous cell carcinoma (SCC) using the novel device line-field confocal optical coherence tomography (LC-OCT).
METHODS
Dermoscopy and LC-OCT images of 73 histopathologically confirmed lesions (46 AKs, 11 BD and 16 SCCs) were included in the study. Exemplary lesions (10 AKs, 5 BD and 5 SCCs) were additionally investigated with optical coherence tomography and reflectance confocal microscopy.
RESULTS
Most common LC-OCT findings of KC in the descriptive statistics were hyperkeratosis/parakeratosis, disruption of stratum corneum, broadened epidermis, basal and suprabasal keratinocyte atypia, dilated vessels/neoangiogenesis and elastosis/collagen alterations. In the univariate multinomial logistic regression, a preserved DEJ was less common in SCC compared with AK and BD, BD displayed marked keratinocyte atypia involving all epidermal layers (bowenoid pattern), while SCC showed ulceration, increased epidermal thickness, keratin plugs, acantholysis, not visible/interrupted DEJ and epidermal bright particles. LC-OCT increased the diagnostic confidence by 24.7% compared with dermoscopy alone.
CONCLUSIONS
Our study describes for the first time specific LC-OCT features of different stages of KC and their histopathological correlates, focusing on keratinocyte morphology and architecture of the epidermis and DEJ. LC-OCT may open new scenarios in the bedside diagnosis, treatment planning and follow-up of KC.
Topics: Bowen's Disease; Humans; Keratinocytes; Keratosis, Actinic; Skin Neoplasms; Tomography, Optical Coherence
PubMed: 34415646
DOI: 10.1111/jdv.17603 -
Annals of Translational Medicine Jan 2022Psoriasis is an immune-mediated chronic, recurrent, inflammatory skin disease. In view of the research on the relationship between stem cells and the pathogenesis of...
BACKGROUND
Psoriasis is an immune-mediated chronic, recurrent, inflammatory skin disease. In view of the research on the relationship between stem cells and the pathogenesis of psoriasis, stem cells may be a new breakthrough in the systemic treatment of psoriasis.
METHODS
The BALB/c mouse psoriasis-like model induced by imiquimod was established and animals were randomly divided into a control group, model group, human umbilical cord mesenchymal stem cells (hUC-MSCs) group with different concentrations (injected separately with umbilical cord stem cells 1×10/kg, 2×10/kg, 4×10/kg through the caudal vein) and fresh hUC-MSCs group (injected with fresh umbilical cord stem cells 2×10/kg through the tail vein). The Psoriasis Area and Severity Index (PASI) score was used to observe the changes in skin lesions. The epidermal thickness, degree of keratinization and infiltration of inflammatory cells were observed by HE staining. The concentrations of -α, -γ, , and other cytokines in serum and skin of mice were measured by enzyme-linked immunosorbent assay (ELISA).
RESULTS
Mice treated with hUC-MSCs showed a good dose-response dependence compared with the control group. As the concentration of hUC-MSCs increased, so did the spleen index. According to the PASI integral trend chart, hUC-MSCs can delay the appearance of skin lesions and accelerate the recovery of skin lesions. HE staining showed that the number of parakeratosis cells in the hUC-MSCs treatment group was significantly decreased, and the degree of dermal hyperplasia and inflammatory cell infiltration in erythrocyte extravasation was significantly lower than in the model group. The higher the concentration of hUC-MSCs, the lower the concentration of the four cytokines in serum and skin tissue.
CONCLUSIONS
hUC-MSCs had an obvious therapeutic effect on imiquimod-induced psoriasis in mice, and a high concentration of hUC-MSCs had the best therapeutic effect. This effect intensity is dose-dependent, and hUC-MSCs at high concentrations have better therapeutic effect.
PubMed: 35282132
DOI: 10.21037/atm-22-4 -
Skin Appendage Disorders Sep 2022
PubMed: 36161080
DOI: 10.1159/000522671 -
Skin Appendage Disorders Feb 2021Granular parakeratosis (GP) is a distinctive acquired keratotic dermatosis that is usually presented with brownish-red hyperkeratotic papules and plaques in the...
Granular parakeratosis (GP) is a distinctive acquired keratotic dermatosis that is usually presented with brownish-red hyperkeratotic papules and plaques in the intertriginous areas. Follicular involvement in GP could be either extending lesions from interfollicular epithelium or originating primarily from the follicular epithelium. The latter was named follicular GP and is considered an extremely rare condition. To our knowledge, there has been one reported case so far in the literature. We herein report the second case of follicular GP in a 52-year-old Thai man presenting with multiple tiny filiform hyperkeratotic papules on his face 2 weeks after using anti-melasma cream. We also propose a classification of GP based on its distinct clinical manifestations and histopathological findings.
PubMed: 33796563
DOI: 10.1159/000512950 -
Cureus Oct 2022Pityriasis rubra pilaris (PRP) is a rare inflammatory papulosquamous skin disease that has six distinct types. Type 5 PRP is called atypical juvenile PRP. Here we report...
Pityriasis rubra pilaris (PRP) is a rare inflammatory papulosquamous skin disease that has six distinct types. Type 5 PRP is called atypical juvenile PRP. Here we report the case of a 17-year-old boy with insignificant past medical history presenting with a history of persistent slowly progressing very itchy skin lesions since the age of seven years. The lesions were photoaggravated. No similar cases in the family were observed and the parents were not consanguint. Skin examination revealed scaly erythematous patches, papules and plaques all over his body. There were also ichthyosiform-like scales covering the whole body. Hair, nails, and mucus membranes examinations were normal. A 4-mm punch skin biopsy was taken. The dermis revealed hyperkeratosis with checkerboard pattern of orthokeratosis and parakeratosis, the granular layer was preserved and acanthosis with thick and short rete ridges. The dermis showed mild perivascular lymphocytic infiltrates. On the basis of the above clinicopathological findings, the diagnosis of pityriasis rubra pilaris (atypical juvenile type) (type 5) was made. The patient was started on isotretinoin capsule 20 mg twice a day and placed under periodic follow-up.
PubMed: 36381776
DOI: 10.7759/cureus.30234