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International Journal of Surgery Case... Jan 2024Pemphigus Vulgaris (PV) is a low incidence autoimmune mucocutaneous bullous disease, in which pathogenic antibodies are directed against the keratinocyte cell surface....
INTRODUCTION AND IMPORTANCE
Pemphigus Vulgaris (PV) is a low incidence autoimmune mucocutaneous bullous disease, in which pathogenic antibodies are directed against the keratinocyte cell surface. Although anal involvement is unusual, correlations between its appearance and disease severity have been recently reported.
CASE PRESENTATION
A 42-year-old male presented with an anal fissure and a year of recurrent oral and pharyngeal aphtha. A chemical sphincterotomy with botulinum toxin plus fissurectomy was performed. 3 years later an upper eyelid injury raised suspicion of pemphigus vulgaris (PV), tested negative for specific antibodies. A couple years later, an anal fissure, and suspected Crohn's disease, led to a second intervention. Surgical analysis unveiled characteristics indicative of a vegetating variant of PV.
CLINICAL DISCUSSION
Anal involvement in PV varies in prevalence, with studies reporting rates between 2 % and 27.98 %. This manifestation often accompanies late disease stages and may indicate severity, notably in association with oral lesions. Patients might not readily discuss anal symptoms, leading to potential underreporting. Anal PV is linked to other lesions (ocular, nasal, genital) and the severity of oral PV. Even when other sites are in remission, anal recurrence can occur. Early recognition and follow-up are crucial, highlighting the need for routine anal examination and confirmatory diagnostics.
CONCLUSION
PV lesions can present on the skin or mucosa, although oral lesions are the most common site of initial presentation. Anal PV is a diagnostic challenge, and this case illustrates the importance of a careful evaluation.
PubMed: 38150999
DOI: 10.1016/j.ijscr.2023.109185 -
The American Journal of Dermatopathology Jun 2024Although many individual cases and small series of toxic erythema of chemotherapy (TEC) have been described, the full spectrum of findings is not well understood.
INTRODUCTION
Although many individual cases and small series of toxic erythema of chemotherapy (TEC) have been described, the full spectrum of findings is not well understood.
OBJECTIVE
To provide a comprehensive review of the clinical and histopathologic features of TEC with an emphasis on novel histopathologic findings.
METHODS
We searched our electronic medical record for "toxic erythema of chemotherapy" or "neutrophilic eccrine hidradenitis." Fifty-six cases meeting clinical and histopathologic criteria were identified. The electronic medical record and accompanying hematoxylin and eosin-stained slides were retrospectively reviewed.
RESULTS
The clinical findings were heterogeneous but included classic presentations such as intertriginous eruptions (34%) and acral erythema (25%). The most common histopathologic features were apoptotic keratinocytes (95%), basal vacuolar change (91%), and epithelial dysmaturation (79%). Eccrine squamous syringometaplasia was seen in over half of the cases (33/56; 59%), whereas neutrophilic eccrine hidradenitis was uncommon (16%). Interestingly, many cases showed prominent interstitial histiocytes (55%). Other novel findings included irregular orthohyperkeratosis (23%), irregular epidermal hyperplasia (14%), and acantholysis (9%).
LIMITATIONS
As a retrospective study, it is subject to information bias.
CONCLUSION
This is the largest reported series of TEC. In addition to confirming previously reported features, we identify novel histopathologic findings to add to the spectrum of TEC.
Topics: Humans; Retrospective Studies; Female; Middle Aged; Male; Drug Eruptions; Aged; Adult; Antineoplastic Agents; Erythema; Young Adult; Hidradenitis; Aged, 80 and over
PubMed: 38133527
DOI: 10.1097/DAD.0000000000002450 -
Cureus Nov 2023Pemphigus vulgaris (PV) is a chronic autoimmune disorder that causes painful blisters on the skin and mucosa along with erosions due to intra-epithelial acantholysis....
Pemphigus vulgaris (PV) is a chronic autoimmune disorder that causes painful blisters on the skin and mucosa along with erosions due to intra-epithelial acantholysis. This acantholysis is mainly due to an immune reaction against desmoglein (an adhesion glycoprotein molecule) by IgG autoantibodies, which causes loss of cell-to-cell adhesion. The treatment consists of systemic corticosteroids such as tablet prednisolone along with topical steroids such as 0.1% triamcinolone paste. But steroids are known for their side effects, one of which is hypertension. It is vital for a dentist to curate the management of this lesion particularly when the drug of choice can potentially lead to adverse effects including systemic complications. This is a case report of a 60-year-old female with PV with systemic hypertension, emphasizing the management of this condition so as to prevent any complications that may arise due to the drug that is administered.
PubMed: 38050527
DOI: 10.7759/cureus.48184 -
Journal of Cutaneous Medicine and... 2024
Topics: Humans; Acitretin; Methotrexate; Acantholysis; Ichthyosis
PubMed: 37991057
DOI: 10.1177/12034754231211567 -
Cureus Oct 2023A 51-year-old uninsured, otherwise healthy male who works in the fishing industry presented with a two-month history of pruritic scaly plaques on his face, scalp, and...
A 51-year-old uninsured, otherwise healthy male who works in the fishing industry presented with a two-month history of pruritic scaly plaques on his face, scalp, and trunk and mild photosensitivity. A biopsy of a scalp lesion revealed acantholysis consistent with pemphigus foliaceus. Laboratory testing demonstrated elevated anti-desmoglein 1, positive antinuclear antibodies (ANA and anti-dsDNA), and elevated Sjögren's anti-SS-A antibodies. The patient was diagnosed with pemphigus erythematosus. The patient was not optimally responsive and was unable to discontinue systemic corticosteroids despite a maximum dosage of mycophenolate mofetil of 3000 mg/day. Hence, rituximab was added as a rescue treatment with the rheumatoid arthritis protocol. Three months after starting rituximab, there was a marked improvement in symptoms with complete resolution of cutaneous lesions.
PubMed: 37954755
DOI: 10.7759/cureus.46910 -
BMC Immunology Nov 2023Glucocorticoids are the first-line treatment for Pemphigus vulgaris (PV), but its serious side effects can be life-threatening for PV patients. Tacrolimus (FK506) has...
BACKGROUND
Glucocorticoids are the first-line treatment for Pemphigus vulgaris (PV), but its serious side effects can be life-threatening for PV patients. Tacrolimus (FK506) has been reported to have an adjuvant treatment effect against PV. However, the mechanism underlying the inhibitory effect of FK506 on PV-IgG-induced acantholysis is unclear.
OBJECTIVE
The objective of this study was to explore the effect of FK506 on desmoglein (Dsg) expression and cell adhesion in an immortalized human keratinocyte cell line (HaCaT cells) stimulated with PV sera.
METHODS
A cell culture model of PV was established by stimulating HaCaT cells with 5% PV sera with or without FK506 and clobetasol propionate (CP) treatment. The effects of PV sera on intercellular junctions and protein levels of p38 mitogen-activated protein kinase (p38MAPK), heat shock protein 27 (HSP27), and Dsg were assayed using western blot analysis, immunofluorescence staining, and a keratinocyte dissociation assay.
RESULTS
PV sera-induced downregulation of Dsg3 was observed in HaCaT cells and was blocked by FK506 and/or CP. Immunofluorescence staining revealed that linear deposits of Dsg3 on the surface of HaCaT cells in the PV sera group disappeared and were replaced by granular and agglomerated fluorescent particles on the cell surface; however, this effect was reversed by FK506 and/or CP treatment. Furthermore, cell dissociation assays showed that FK506 alone or in combination with CP increased cell adhesion in HaCaT cells and ameliorated loss of cell adhesion induced by PV sera. Additionally, FK506 noticeably decreased the PV serum-induced phosphorylation of HSP 27, but had no effect on p38MAPK phosphorylation.
CONCLUSION
FK506 reverses PV-IgG induced-Dsg depletion and desmosomal dissociation in HaCaT cells, and this effect may be obtained by inhibiting HSP27 phosphorylation.
Topics: Humans; Pemphigus; Tacrolimus; HSP27 Heat-Shock Proteins; HaCaT Cells; Phosphorylation; Keratinocytes; Desmoglein 3; Immunoglobulin G; Autoantibodies
PubMed: 37940861
DOI: 10.1186/s12865-023-00582-z -
Acta Dermatovenerologica Croatica : ADC Aug 2023Dear Editor, Pemphigus vegetans (PV) of Hallopeau is a rare and indolent variant of pemphigus clinically characterized by vegetating lesions preceded by pustules mainly...
Dear Editor, Pemphigus vegetans (PV) of Hallopeau is a rare and indolent variant of pemphigus clinically characterized by vegetating lesions preceded by pustules mainly in flexural areas (1,2). This helps us to differentiate it from PV of Neumann, which is a more extensive and refractory disease, more alike to a pemphigus vulgaris outbreak with blisters which turn into vegetating plaques (3). We report the clinical presentation, course, and therapeutic response in a patient diagnosed with PV of Hallopeau from its early stage during a 3-year follow up. A 62-year-old man, non-smoker, presented at our clinic in July 2018 with hemorrhagic-serous crusts and fissures on the vermilion of the lower lip (Figure 1, a) and two merged circinate, sharply demarcated plaques on the right side of the groin (Figure 1, b). Plaque margins were elevated, with hypertrophic granulation tissue studded with pustules. Mucosal and cutaneous lesions persisted 6 and 4 weeks, respectively. The rest of the mucosa and skin were unaffected; the general state was good. The patient's family history for skin diseases was negative. The medical history included hypertension, atherosclerosis and hypercholesterolemia, hiatus hernia, and recent surgery (3 months prior) of an aortic abdominal aneurysm with reconstruction and synthetic graft placement. He was taking antihypertensives (fixed combination of 3 drugs, among them the ACE-inhibitor perindopril) with well-regulated blood pressure, statins, a pump-proton inhibitor, and acetylsalicylic acid. Differential blood count revealed eosinophilia. Histopathology finding showed acanthosis, suprabasal clefting with a suprabasilar bulla and acantholysis, prominent eosinophilic intraepidermal spongiosis, and heavy dermal infiltration of eosinophils and lymphocytes (Figure 2, a and b). The diagnosis of pemphigus was confirmed by direct immunofluorescence (DIF), which detected C3 deposits on the surface of keratinocytes throughout the epidermis of perilesional skin. Circulating pemphigus antibodies were detected by indirect IF. Only Dsg 3 antibodies were detected using an ELISA assay (233.23 RU/mL). After establishing the diagnosis of PV of Hallopeau, treatment with prednisolone 0.75 mg/kg/day orally in combination with adjuvant immunosuppression (azathioprine 100 mg daily) was started. Appropriate topical therapy with local steroids and antiseptic was applied. The steroid dose was titrated and gradually tapered down to the minimum required to control the disease - 10 mg. One-year remission was achieved. Azathioprine was withdrawn in October 2019 and since then the patient experienced a flare-up twice. The control of pemphigus flare-ups was achieved by a low dose of steroids (30 mg prednisolone orally). It remains debatable whether surgical trauma and radiology procedures such as angiographies (4) well as ACE-inhibitor drugs (5) triggered or aggravated the pemphigus. Early recognition and correct diagnosis of this rare type of pemphigus allows us to treat and control the disease successfully with lower doses of steroids, reducing complications to the minimum.
Topics: Male; Humans; Middle Aged; Pemphigus; Azathioprine; Skin; Eosinophilia; Blister; Prednisolone; Steroids
PubMed: 37843091
DOI: No ID Found -
Case Reports in Women's Health Sep 2023Darier disease is an autosomal dominant disorder with hyperkeratotic papules affecting primarily seborrheic areas of the upper chest, back, forehead, scalp, nasolabial...
Darier disease is an autosomal dominant disorder with hyperkeratotic papules affecting primarily seborrheic areas of the upper chest, back, forehead, scalp, nasolabial folds, ears, and, less frequently, the oral mucosa. A typical eruption consists of keratotic and crusted skin-colored papules and plaques. Pruritus occurs in 80% of patients, and pain is rare. Lesions can be triggered by exposure to ultraviolet light, heat, or stress. Secondary infections of the lesions are a common complication. A definitive diagnosis is obtained by a biopsy showing histological features such as acantholysis, suprabasal clefts, and "corps rond and grains". Here we present a 37-year-old woman admitted to the gynecology department with pruritic lesions she had noticed on her vulva and perineum for three months. A vulvar biopsy led to the diagnosis of Darier disease. She was referred to the dermatology department and treated with oral acitretin since systemic retinoids are offered as the first-line treatment of the disease.
PubMed: 37753222
DOI: 10.1016/j.crwh.2023.e00545 -
Drug Design, Development and Therapy 2023Thalidomide (Tha) can be used as a selective treatment for mild pemphigus vulgaris (PV). However, the specific mechanism of action remains unclear.
PURPOSE
Thalidomide (Tha) can be used as a selective treatment for mild pemphigus vulgaris (PV). However, the specific mechanism of action remains unclear.
PATIENTS AND METHODS
PV IgG extracted from patients' serum was cocultured with HaCaT cells to construct a PV cell model, and different concentrations of Tha were used to screen the drug effect. The expression level of MYD88 was assessed in skin lesions of PV patients. Intracellular Ca concentration, reactive oxygen species level, DSG3, PG, MYD88, apoptosis-related proteins (Caspase-3, Bcl-2, and Bax), NF-κB pathway-related proteins (IκBα, p-IκBα, p50, and p65), NLRP3, IFN-γ, TNF-α, IL-6, and IL-8 levels were measured. PV IgG was subcutaneously injected into C57BL/6 neonatal mice to construct the animal model. Immunofluorescence was used to detect IgG deposition in the mouse epidermis, whereas immunohistochemistry and TUNEL methods were used to detect the expression of MYD88 and NLRP3 as well as cell apoptosis level in the mouse epidermis.
RESULTS
Tha reversed the decrease in Dsg3 and PG caused by PV IgG. The expression of MyD88 increased in the patients' skin, PV cell model, and PV mouse model. The increase in MyD88 expression level in PV cell models and PV newborn mouse models was inhibited by Tha. Overexpression of MyD88 induced a decrease in the expression levels of Dsg3 and PG in Hacat cells. Overexpression of MyD88 inhibited Tha effects on Dsg3 and PG expressions and blocked Tha effects on Ca, apoptosis, Bax, Bcl-2, and Caspase-3 expressions, oxidative damage, and inflammatory response in HaCat cells. Tha alleviated acantholysis induced by PV IgG in model mice.
CONCLUSION
Through MYD88, Tha attenuated apoptosis of HaCat cells, modulated NF-κB to hamper the oxidative damage and inflammatory response in the PV cell models, and alleviated acantholysis, IgG deposition, and epidermal cell apoptosis induced by PV IgG in model mice.
Topics: Animals; Humans; Mice; Acantholysis; Animals, Newborn; Apoptosis; bcl-2-Associated X Protein; Caspase 3; HaCaT Cells; Immunoglobulin G; Inflammation; Mice, Inbred C57BL; Myeloid Differentiation Factor 88; NF-kappa B; NF-KappaB Inhibitor alpha; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Pemphigus; Thalidomide
PubMed: 37719363
DOI: 10.2147/DDDT.S407242 -
The Journal of Investigative Dermatology Feb 2024Desmosomes are dynamic complex protein structures involved in cellular adhesion. Disruption of these structures by loss-of-function variants in desmosomal genes leads to...
Desmosomes are dynamic complex protein structures involved in cellular adhesion. Disruption of these structures by loss-of-function variants in desmosomal genes leads to a variety of skin- and heart-related phenotypes. In this study, we report TUFT1 as a desmosome-associated protein, implicated in epidermal integrity. In two siblings with mild skin fragility, woolly hair, and mild palmoplantar keratoderma but without a cardiac phenotype, we identified a homozygous splice-site variant in the TUFT1 gene, leading to aberrant mRNA splicing and loss of TUFT1 protein. Patients' skin and keratinocytes showed acantholysis, perinuclear retraction of intermediate filaments, and reduced mechanical stress resistance. Immunolabeling and transfection studies showed that TUFT1 is positioned within the desmosome and that its location is dependent on the presence of the desmoplakin carboxy-terminal tail. A Tuft1-knockout mouse model mimicked the patients' phenotypes. Altogether, this study reveals TUFT1 as a desmosome-associated protein, whose absence causes skin fragility, woolly hair, and palmoplantar keratoderma.
Topics: Animals; Humans; Mice; Desmoplakins; Desmosomes; Hair; Hair Diseases; Keratoderma, Palmoplantar; Skin; Skin Abnormalities
PubMed: 37716648
DOI: 10.1016/j.jid.2023.02.044