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Naunyn-Schmiedeberg's Archives of... Mar 2024Clostridium botulinum C3 exoenzyme (C3bot) exclusively inhibits RhoA, B and C by ADP-ribosylation and is therefore used as a cell-permeable tool for investigating the...
Clostridium botulinum C3 exoenzyme (C3bot) exclusively inhibits RhoA, B and C by ADP-ribosylation and is therefore used as a cell-permeable tool for investigating the cellular role of these Rho-GTPases. Rho-GTPases represent a molecular switch integrating different receptor signalling to downstream cascades including transcriptional cascades that regulate various cellular processes, such as regulation of actin cytoskeleton and cell proliferation. C3bot-induced inhibition of RhoA leads to reorganization of the actin cytoskeleton, morphological changes, and inhibition of cell proliferation as well as modulation of inflammatory response. In this study, we characterized the C3bot-mediated effects on a full-thickness skin model exhibiting a psoriasis-like phenotype through the addition of cytokines. Indeed, after the addition of cytokines, a decrease in epidermal thickness, parakeratosis, and induction of IL-6 was detected. In the next step, it was studied whether C3bot caused a reduction in the cytokine-induced psoriasis-like phenotypes. Basal addition of C3bot after cytokine induction of the full-thickness skin models caused less epidermal thinning and reduced IL-6 abundance. Simultaneous basal incubation with cytokines and C3bot, IL-6 abundance was inhibited, but epidermal thickness was only moderately affected. When C3bot was added apically to the skin model, IL-6 abundance was reduced, but no further effects on the psoriasis-like phenotype of the epidermis were observed. In summary, C3bot inhibits the cytokine-induced expression of IL-6 and thus may have an impact on the pro-inflammatory immune response in the psoriasis-like phenotype.
Topics: Humans; Clostridium botulinum; Botulinum Toxins; Interleukin-6; ADP Ribose Transferases; Phenotype; rho GTP-Binding Proteins; Psoriasis
PubMed: 37707681
DOI: 10.1007/s00210-023-02718-9 -
International Journal of Dermatology Feb 2024Plaque psoriasis is relatively straightforward to identify. When diagnostic concerns arise in atypical cases, a biopsy is needed. It is widely accepted that the Munro...
BACKGROUND
Plaque psoriasis is relatively straightforward to identify. When diagnostic concerns arise in atypical cases, a biopsy is needed. It is widely accepted that the Munro microabscess and the spongiform pustule of Kogoj are diagnostic pathological features. However, the diagnostic dilemma is likely to arise in cases without these specific pathological changes and typical clinical features. This study aimed to investigate clinical and pathological clues in distinguishing atypical plaque psoriasis from its mimics.
METHODS
We evaluated the clinicopathological features of 20 cases of atypical plaque psoriasis and 40 cases of psoriasis mimics as controls including pityriasis rosea (n = 10), pityriasis lichenoides chronica (n = 8), and subacute dermatitis (n = 22).
RESULTS
A retrospective analysis of the clinicopathological characteristics of patients with atypical plaque psoriasis and controls was performed. Pathologically, there were significant differences between the two groups in the types of parakeratosis (P = 0.046), epidermal capture of extravasated erythrocytes (P = 0.011), focal basal liquefied degeneration (P = 0.017), types of inflammatory cells (P = 0.000), and depth of inflammation (P = 0.000). Clinically, we found the presence of scales and crusts was significantly different between the two groups.
CONCLUSION
This study offers insight into the clinicopathological features of atypical plaque psoriasis. These differential diagnostic features, compared with its mimics, are proposed to assist the clinician in the diagnosis and treatment of atypical plaque psoriasis.
PubMed: 38366678
DOI: 10.1111/ijd.17063 -
Explore (New York, N.Y.) 2023Immune checkpoint inhibitors (ICIs) have emerged as a revolutionary therapy in advanced squamous non-small cell lung cancer (sqNSCLC) and ushered a new era of... (Review)
Review
BACKGROUND
Immune checkpoint inhibitors (ICIs) have emerged as a revolutionary therapy in advanced squamous non-small cell lung cancer (sqNSCLC) and ushered a new era of immunotherapy. Despite of remarkable outcomes, a wide spectrum of immune-related adverse events (irAEs) was reported, among which cutaneous reactions were the most common. Cutaneous irAEs were mainly managed by glucocorticoids, whereas prolonged use of glucocorticoids may cuase kinds of side effects, especially in elderly paitients, and diminish the anti-tumor efficacy of ICIs, thus finding a safe and effective alternative approach to managing cutaneous irAEs is imperative.
CASE SUMMARY
A 71-year-old man who was diagnosed with advanced sqNSCLC suffered from sporadic maculopapulars one week later after the fifth cycle of sintilimab treatment, and the skin lesions had been deteriorating rapidly. Skin biopsy revealed epidermal parakeratosis with a dense band-like lymphocytic infiltrate and acanthosis, indicating a diagnosis of immune-induced lichenoid dermatitis. Oral administration of traditional Chinese herbal formula modified Weiling decoction significantly alleviated the symptoms of the patient. The dosage of Weiling decoction were maintained for about three months without recurrence of cutaneous adverse reactions and any other side effects. The patient refused to receive further anti-tumor medication and stayed alive without disease progression at follow up.
CONCLUSION
We present modified Weiling decoction successfully ameliorates immune-induced lichenoid dermatitis in a patient with sqNSCLC for the first time. This report indicates that Weiling decoction may be an effective and safe complementary or alternative approach for the treatment of cutaneous irAEs. Further investigation of the underling mechanism is required in the future.
Topics: Male; Humans; Aged; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Antineoplastic Agents, Immunological; Skin; Drug-Related Side Effects and Adverse Reactions; Dermatitis; Retrospective Studies
PubMed: 36878772
DOI: 10.1016/j.explore.2023.02.008 -
International Journal of Dermatology May 2024
PubMed: 38757634
DOI: 10.1111/ijd.17253 -
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 -
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 -
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 -
Journal of Lower Genital Tract Disease Apr 2024Lichen planus (LP) and lichen sclerosus (LS) are the most common vulvar lichenoid dermatoses. The diagnostic challenges are due to site-specific variation in microscopic...
OBJECTIVES
Lichen planus (LP) and lichen sclerosus (LS) are the most common vulvar lichenoid dermatoses. The diagnostic challenges are due to site-specific variation in microscopic appearance and small-sized biopsies. Authentication of diagnostic criteria to distinguish LS and LP to uncover any resemblance or divergence in presentation of these conditions is attempted.
METHODS
Cases of vulvar LP and LS diagnosed between January 2012 to December 2022 were included. The clinical details included age, presenting symptoms, examination findings, and other organ involvement. Histopathological analysis of epidermal, dermal, and adnexal findings was done.
RESULTS
There were 28 cases of vulvar LP and 72 cases of LS, with a median age of 51 and 60 years, respectively. Depigmentation and atrophy were the major clinical features in LS, whereas ulcers/erosions and erythema were more prevalent in LP with a significantly higher incidence of oral involvement. The most diagnostic feature in LS was diffuse dermal sclerosis (76.8%) and interstitial pattern of inflammation (81.4%), whereas the characteristic features in LP cases was a lichenoid pattern of inflammation (85.7%), necrotic keratinocytes, and lymphocytic exocytosis. In 44.4% of LS, unconventional features like compact orthokeratosis, parakeratosis, thickened/wedge-shaped hypergranulosis, and sawtooth rete pegs were noted. Lichen sclerosus with lichenoid inflammation (21.4%) mimicked LP, from which it was distinguished by presence of thickened or diminished granular layer with basal melanin absence (60%) and dermal homogenization (80%).
CONCLUSION
Although the classical, well-established variant of LS poses no diagnostic difficulty, the unconventional variant may mimic LP. Identification of the subtle histological clues demonstrated in this study can help to arrive at the correct diagnosis.
Topics: Female; Humans; Middle Aged; Lichen Sclerosus et Atrophicus; Vulva; Lichen Planus; Inflammation; Biopsy; Vulvar Lichen Sclerosus
PubMed: 38518217
DOI: 10.1097/LGT.0000000000000789 -
Lupus Feb 2024Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease that can manifest itself with a variety of skin symptoms. Periorbital erythema, a rare variant of CLE,...
Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease that can manifest itself with a variety of skin symptoms. Periorbital erythema, a rare variant of CLE, presents challenges in terms of diagnosis and treatment. Here, we report a case of CLE presenting with periorbital erythema and edema. A 42-year-old female patient presented with complaints of erythema, edema, and scaling on the right eyelid that started four months ago. A skin biopsy was performed on the lesioned skin of the eyelid to differentiate dermatomyositis, cutaneous lupus erythematosus, sarcoidosis, lupus vulgaris, and cutaneous lymphoma. Histopathological examination revealed focal hyperkeratosis and parakeratosis on the surface of the epidermis, vacuolar degeneration in the basal layer of the epidermis, lymphocyte exocytosis with necrotic keratinocytes, edema in the dermis, melanophages, and perivascular, periadnexal lymphocytic reaction. Laboratory tests showed negative antinuclear antibody and anti-dsDNA, but positivity for anti-Ro-52. In the absence of any other complaints, the patient was diagnosed with cutaneous lupus erythematosus presenting with periorbital erythema based on clinical, histopathological, and laboratory findings. Hydroxychloroquine 200 mg/day, topical corticosteroid, and topical tacrolimus were administered. Two months later, significant improvement in the lesions was observed. In conclusion, it should be kept in mind that periorbital erythema can develop as a rare variant of CLE and can be misdiagnosed as contact dermatitis, dermatomyositis, sarcoidosis, or cutaneous lymphoma. Additionally, the ANA and anti-dsDNA antibodies are often found to be negative in these cases. In establishing the diagnosis, firstly considering the disease, followed by histopathological examinations and laboratory tests, is crucial.
Topics: Female; Humans; Adult; Dermatomyositis; Lupus Erythematosus, Systemic; Erythema; Lupus Erythematosus, Cutaneous; Skin Neoplasms; Edema; Lymphoma; Sarcoidosis
PubMed: 38148123
DOI: 10.1177/09612033231224767 -
Porcine Health Management Feb 2024The complex aetiology of gastric lesions in pigs remains largely unknown and effective preventive measures and pharmaceutical treatment of the disease have not been...
BACKGROUND
The complex aetiology of gastric lesions in pigs remains largely unknown and effective preventive measures and pharmaceutical treatment of the disease have not been developed yet. Regardless of the fact that the overwhelming majority of previous research works dealing with gastric ulceration in pigs focused on the role of the nutritional determinants, including chemical composition of feeds, cereal type, finely ground pelleted diets, and feed additives, conclusions presented therein remain highly ambiguous. Thus, the purpose of this study was to evaluate the impact of the disease on production performance, and investigate the influence of selected non-dietary risk factors on the prevalence of gastric alterations in finishing pigs reared under conditions of 11 modern farms located in Poland.
RESULTS
A total number of 26,043 finishing pigs was examined. 15,228 (58.47%) had gastric ulcers. Intact stomachs were detected in 6176 animals (23.71%). Parakeratosis and erosion were observed in 2551 (9.80%) and 2088 (8.02%), respectively. Among eight continuous variables two were found to be significantly associated with prevalence of the gastric ulcer: the growing number of animals in the herd, which was negatively correlated (P = 0.002; ρ = -0.37), and the growing average entry weight of animals transported to the finisher farm (P = 0.047; ρ = 0.24), which increased the risk of gastric ulcers prevalence. Among 12 nominal variables, problems with the quality of farm management (P = 0.041), and usage of straw as a bedding material (P = 0.002) were identified as determinants significantly associated with occurrence of the analysed health problem.
CONCLUSIONS
Among 20 non-nutritional variables analysed in our study only few factors were found to be associated with the prevalence of the disease. The impact of broadly understood management issues on gastric health in finishing pigs deserves further research.
PubMed: 38409105
DOI: 10.1186/s40813-024-00362-0