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Acta Dermatovenerologica Croatica : ADC Nov 2022Dear Editor, Segmental Darier disease (DD) is a rare disease with around 40 described English literature cases. It is hypothesized that one of the causes of the disease...
Dear Editor, Segmental Darier disease (DD) is a rare disease with around 40 described English literature cases. It is hypothesized that one of the causes of the disease is a post-zygotic somatic mutation for the calcium ATPase pump, only present in lesional skin. There are two types of segmental DD: type 1, where lesions follow Blaschko's lines unilaterally, and type 2, characterized by focal areas of increased severity in patients with generalized DD (1). Type 1 segmental DD is not easily diagnosed due to the lack of positive family history, the late onset of the disease in the third or fourth decade of life, and lack of DD-associated features. The differential diagnosis of type 1 segmental DD includes acquired papular dermatoses distributed in linear or zosteriform fashion, such as lichen planus, psoriasis, lichen striatus, or linear porokeratosis (2). We report two cases of segmental DD, of which the first case was a 43-year-old woman who presented with pruritic skin changes five years in duration and a history of seasonal aggravation. On examination, light brownish to reddish keratotic small papules were observed on the left abdomen and inframammary area, arranged in a swirling pattern (Figure 1, a). Dermoscopy showed polygonal or roundish yellowish/brown areas surrounded with whitish structureless areas (Figure 1, b). The histopathological correlations for dermoscopic brownish polygonal or round areas are hyperkeratosis, parakeratosis, and dyskeratotic keratinocytes, which were present in the biopsy specimen (Figure 1, c). The patient was prescribed 0.1% tretinoin gel, which led to marked improvement (Figure 1, d). The second case was a 62-year-old woman who presented with a flare of small red-brown papules, eroded papules, and some yellowish crusts arranged in a zosteriform pattern on the right side of the upper abdomen (Figure 2, a). Dermoscopy showed polygonal, roundish, yellowish areas surrounded with whitish and reddish structureless areas (Figure 2, b). Histopathology mainly revealed compact orthokeratosis and small foci of parakeratosis, marked granular layer with dyskeratotic keratinocytes, and foci of suprabasal acantholysis consistent with the diagnosis of DD (Figure 2, d, d). The patient was prescribed topical steroid cream and 0.1% adapalene cream, which also led to improvement. In both of our cases, a final diagnosis of type 1 segmental DD was established based on clinico-histopathologic correlation, since acantholytic dyskeratotic epidermal nevus could not have been ruled out only based on the histopathology report as it is clinically and histologically indistinguishable from segmental DD. However, the late age of onset and aggravation resulting from external factors such as heat, sunlight, and sweat supported the diagnosis of segmental DD. Although the final diagnosis of type 1 segmental DD is typically established based on clinico-histopathological correlation, we find dermoscopy particularly useful in aiding the diagnosis by eliminating differential diagnoses and being aware of their well-known dermoscopic patterns.
Topics: Female; Humans; Adult; Middle Aged; Darier Disease; Parakeratosis; Dermoscopy; Skin
PubMed: 36812281
DOI: No ID Found -
Dermatopathology (Basel, Switzerland) Feb 2023Post-pemphigus acanthomas have been rarely discussed in the literature. A prior case series identified 47 cases of pemphigus vulgaris and 5 cases of pemphigus foliaceus,...
Post-pemphigus acanthomas have been rarely discussed in the literature. A prior case series identified 47 cases of pemphigus vulgaris and 5 cases of pemphigus foliaceus, out of which 13 developed acanthomata as a part of the healing process. Additionally, a case report by Ohashi et al. reported similar recalcitrant lesions on the trunk of a patient with pemphigus foliaceus being treated with prednisolone, IVIG, plasma exchange, and cyclosporine. Some view post-pemphigus acanthomas as variants of hypertrophic pemphigus vulgaris, being difficult to diagnose when they present as only single lesions, with a clinical differential of an inflamed seborrheic keratosis or squamous cell carcinoma. Here, we present a case of a 52-year-old female with a history of pemphigus vulgaris and four months of only topical therapy (fluocinonide 0.05%) who presented with a painful, hyperkeratotic plaque on the right mid-back that was found to be a post-pemphigus acanthoma.
PubMed: 36810570
DOI: 10.3390/dermatopathology10010012 -
JNMA; Journal of the Nepal Medical... Jul 2022Pemphigus vulgaris is a rare autoimmune mucocutaneous blistering disease clinically presenting as vesicles, bullae, and erosion and histologically characterized by...
UNLABELLED
Pemphigus vulgaris is a rare autoimmune mucocutaneous blistering disease clinically presenting as vesicles, bullae, and erosion and histologically characterized by suprabasal split and acantholysis. It usually affects mucous membranes and skin. Recurrent oral ulcers can only be the clinical manifestation before progressing into skin lesions. This can lead to the delayed diagnosis of this disease. Here we report a case of pemphigus vulgaris which was diagnosed after years of suffering from an oral ulcer that eventually progressed to widespread skin blistering and ulceration. The patient was treated with oral prednisolone which showed improvement within a week. Physicians should consider the differential diagnosis of pemphigus vulgaris in patients presenting with a recurrent oral ulcer.
KEYWORDS
delayed diagnosis; oral ulcer; pemphigus vulgaris.
Topics: Humans; Pemphigus; Oral Ulcer; Delayed Diagnosis; Prednisolone; Skin
PubMed: 36705190
DOI: 10.31729/jnma.7594 -
The British Journal of Dermatology Jan 2023Desmosomes are complex cell junction structures that connect intermediate filaments providing strong cell-to-cell adhesion in tissues exposed to mechanical stress.
BACKGROUND
Desmosomes are complex cell junction structures that connect intermediate filaments providing strong cell-to-cell adhesion in tissues exposed to mechanical stress.
OBJECTIVES
To identify causal variants in individuals with woolly hair and skin fragility of unknown genetic cause.
METHODS
This research was conducted using whole-genome sequencing, whole-exome sequencing, clinical phenotyping, haplotype analysis, single-cell RNA sequencing data analysis, immunofluorescence microscopy and transmission electron microscopy.
RESULTS
We identified homozygous predicted loss-of-function tuftelin-1 (TUFT1) variants in nine individuals, from three families, with woolly hair and skin fragility. One donor splice-site variant, c.60+1G>A, was present in two families, while a frameshift variant, p.Gln189Asnfs*49, was found in the third family. Haplotype analysis showed the c.60+1G>A substitution to be a founder variant in the Irish population that likely arose approximately 20 generations ago. Human and mouse single-cell RNA sequencing data showed TUFT1 expression to be enriched in the hair dermal sheath and keratinocytes. TUFT1 expression was highly correlated with genes encoding desmosomal components implicated in diseases with phenotypes that overlap with the cohort presented here. Immunofluorescence showed tuftelin-1 to be mainly localized to the peripheral cell membranes of keratinocytes in normal skin. Skin samples from individuals with TUFT1 variants showed markedly reduced immunoreactivity for tuftelin-1, with a loss of the keratinocyte cell membrane labelling. Light microscopy revealed keratinocyte adhesion, mild hyperkeratosis and areas of superficial peeling. Transmission electron microscopy showed panepidermal acantholysis with widening of intercellular spaces throughout the epidermis and desmosomal detachment through the inner plaques.
CONCLUSIONS
Biallelic loss-of-function TUFT1 variants cause a new autosomal recessive skin/hair disorder characterized by woolly hair texture and early-onset skin fragility. Tuftelin-1 has a role in desmosomal integrity and function.
Topics: Humans; Mice; Animals; Hair Diseases; Skin; Skin Abnormalities; Keratinocytes; Hair
PubMed: 36689522
DOI: 10.1093/bjd/ljac026 -
Journal of Cutaneous Pathology Aug 2023Pemphigus is a potentially life-threatening autoimmune blistering disease. To date, studies assessing the association of histopathology with clinical phenotype are...
INTRODUCTION
Pemphigus is a potentially life-threatening autoimmune blistering disease. To date, studies assessing the association of histopathology with clinical phenotype are lacking. We sought to evaluate the main histopathologic findings and, also, the potential links between cutaneous inflammatory infiltrates and clinical characteristics in pemphigus.
METHODS
We conducted a retrospective cohort study in patients diagnosed with pemphigus vulgaris (PV) and pemphigus foliaceus (PF) in a referral center for autoimmune blistering diseases.
RESULTS
A total of 124 patients were included in the study (97 had PV and 27 had PF). On biopsy specimens, PV was more frequently associated with the "row of tombstones" feature (36.1% vs. 11.1%, p = 0.013), and PF was associated with acanthosis (44.4% vs. 23.7%, p = 0.034). Acantholysis was found in the upper half of the epidermis in PF (96.3% vs. 5.15%, p < 0.001), as opposed to the lower half in PV (75.2% vs. 0%, p = 0.002). Patients with lymphocyte-predominant inflammatory infiltrates in lesional skin specimens presented with a higher frequency of the mucosal-dominant phenotype (25.5% vs. 9.1%, p = 0.014), higher-density cellular infiltrate (100% vs. 41.6%, p < 0.001), and more frequent acantholytic cells (42.6% vs. 23.4%, p = 0.025). Neutrophil-predominant infiltrates in specimens from lesional skin were linked to a milder disease based on median Pemphigus Disease Area Index (38.9% vs. 13.2%, p = 0.036) and Autoimmune Bullous Skin Disorder Intensity Score (20.2 vs. 36.3, p = 0.019), while eosinophil-predominant inflammatory infiltrates were more often associated with eosinophilic spongiosis (100% vs. 23.1%, p = 0.014).
CONCLUSIONS
Lymphocyte-predominant infiltrates in lesional skin specimens of pemphigus patients predict a mucosal-dominant phenotype, while neutrophil-predominant infiltrates are associated with a milder disease.
Topics: Humans; Pemphigus; Retrospective Studies; Skin; Skin Diseases; Blister; Phenotype; Lymphocytes; Autoantibodies
PubMed: 36680509
DOI: 10.1111/cup.14395 -
Journal of Cutaneous Pathology Jun 2023Immune checkpoint inhibitor (ICI)-induced bullous pemphigoid (BP) and Grover disease (GD) are uncommon, and concomitant GD and BP is rarer still. We report a third case...
Immune checkpoint inhibitor (ICI)-induced bullous pemphigoid (BP) and Grover disease (GD) are uncommon, and concomitant GD and BP is rarer still. We report a third case of concomitant BP and GD associated with nivolumab with emphasis on the clinical, histopathologic and immunofluorescence findings as well as differential diagnoses. A 73-year-old male with metastatic renal cell carcinoma on nivolumab developed erythematous scaly papules on the trunk with biopsy showing suprabasal acantholysis with dyskeratosis, consistent with GD. Subsequently, he developed widespread lesions on arms, legs, trunk, and scrotum with new vesiculobullae and urticarial lesions. Biopsy of a vesicle showed subepidermal blister with numerous eosinophils and neutrophils, and immunofluorescence and serological studies were supportive of BP. He continued to have clinically apparent GD that was confirmed on repeat biopsy. The patient was diagnosed with concomitant GD and BP induced by nivolumab and successfully treated with dupilumab. The relationship between ICI-induced GD and BP is not well understood; it has been suggested that T-cell activation against the BP180 antigen expressed on surface of tumor cells may predispose susceptible individuals to BP. Subsequent ICI-induced GD may create keratinocyte injury needed to expose additional proteins to reactivated and autoreactive T-cells, leading to autoimmunity. An important differential diagnosis is bullous GD, which can be distinguished by negative immunofluorescence and serological studies.
Topics: Male; Humans; Aged; Pemphigoid, Bullous; Acantholysis; Nivolumab; Carcinoma, Renal Cell; Kidney Neoplasms; Blister
PubMed: 36601731
DOI: 10.1111/cup.14383 -
Indian Journal of Dermatology 2022Pemphigus is a group of auto-immune blistering disorders, characterised clinically by mucocutaneous blisters and erosions and histopathologically by intra-epidermal...
BACKGROUND
Pemphigus is a group of auto-immune blistering disorders, characterised clinically by mucocutaneous blisters and erosions and histopathologically by intra-epidermal acantholysis. It was traditionally associated with high morbidity and mortality. The use of rituximab has brought upon a new dawn in the treatment of pemphigus.
AIM
A retrospective analysis to ascertain the efficacy, tolerance, adverse effect profile, remission, and relapse with the use of rituximab.
MATERIAL AND METHODS
A retrospective analysis of all diagnosed pemphigus patients who received rituximab therapy over a period of 3 years was performed. The patient's baseline characteristics, disease duration, clinical presentations, mucosal involvement, disease-severity assessment, and adverse events with rituximab were noted. The outcomes were evaluated based on the definitions of the disease-outcome parameters as early and late endpoints.
RESULTS
Of the 17 pemphigus patients, there were 14 females (82.4%) and three males (17.6%) with a mean age of 35.9 ± 16.5 years (range: 9-65 years). Pemphigus vulgaris (PV) was the predominant type in 11 (64.7%) patients. After rituximab infusion, the 17 patients attained the end of consolidation phase (ECP) within 15 days to 3 months, and the mean duration was 1.24 months. The complete remission (CR on/off) ranged from 0.5 to 35 months, and the mean duration of remission was 21.7 months. Within a median time of 4.2 months, almost 80% patients achieved CR on therapy. Nine (53%) patients were in CR without any therapy till the end of the study period, and eight (47%) were in remission while on minimal therapy.
CONCLUSION
Rituximab is an efficacious therapeutic agent for pemphigus and is better tolerated and safer to all the previous medications used in the treatment.
PubMed: 36578732
DOI: 10.4103/ijd.ijd_169_22 -
Clinical Case Reports Dec 2022The anal region is an unusual site of Hailey-Hailey disease. It manifests with lichenoid lesions with crusted erosions around the anus. It should be differentiated from...
The anal region is an unusual site of Hailey-Hailey disease. It manifests with lichenoid lesions with crusted erosions around the anus. It should be differentiated from condylomata acuminata, extramammary Paget disease, and bowenoid papulosis.
PubMed: 36514472
DOI: 10.1002/ccr3.6702 -
Journal of Cutaneous Pathology Jun 2023Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma that may occasionally present divergent histopathologic features. We present two cases of...
Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma that may occasionally present divergent histopathologic features. We present two cases of MCC demonstrating ductal differentiation, one on the lower lip of an 81-year-old man and another on the right forearm of a 67-year-old man. The histopathologic features included TTF1-negative, infiltrative, high-grade basaloid tumor with paranuclear punctate positivity for cytokeratin (CK) 20 and synaptophysin. Rare luminal structures lined by atypical epithelioid cells positive for CEA and CK19 were noted, confirming the presence of ductal differentiation. Although the ductal differentiation is unusual, other histopathologic features and the immunohistochemical profile supported the diagnosis of MCC. Like most divergent features, ductal differentiation is rare in MCC and typically constitutes a very small proportion of the tumor, and is therefore under-recognized. Although the clinical significance of this feature is unclear, recognition and documentation of ductal differentiation and distinguishing it from other mimics such as acantholysis within squamous nests and entrapped eccrine ducts is essential to determine its clinical significance. We also discuss the differential diagnoses of cutaneous basaloid neoplasms with ductal differentiation.
Topics: Male; Humans; Aged, 80 and over; Aged; Carcinoma, Merkel Cell; Skin Neoplasms; Diagnosis, Differential; Cell Differentiation
PubMed: 36454019
DOI: 10.1111/cup.14372 -
Frontiers in Medicine 2022Pemphigus is a chronic autoimmune skin blistering disease, characterized by acantholysis and by the production of autoantibodies directed against the structural...
Pemphigus is a chronic autoimmune skin blistering disease, characterized by acantholysis and by the production of autoantibodies directed against the structural desmosomal proteins desmoglein 1 (DSG1) and/or DSG3. Model systems allow the identification and testing of new therapeutic targets. Here, we evaluated ultrastructural desmosomal morphology in the human skin organ culture (HSOC) model injected with either anti-desmoglein (DSG) 1/3 single-chain variable fragment (scFv, termed Px4-3), Staphylococcus aureus exfoliative toxin (ETA) as a reference and positive control, and normal human IgG as a negative control. Each experimental condition was evaluated in abdominal skin biopsies from five different donors. After 24 h of incubation, we processed the samples for histological and ultrastructural electron microscopy analyses. We found that Px4-3 or ETA induced a loss of desmosomes and increased interdesmosomal widening, similar to patient skin biopsies and other pemphigus models. Thus, we propose the HSOC pemphigus model as an attractive tool to unravel novel therapeutic targets.
PubMed: 36452895
DOI: 10.3389/fmed.2022.997387