Localized pemphigus vulgaris on scalp: an atypical presentation.

We present two middle-aged patients with pruritic, crusted scalp erosions. Skin biopsy showed epidermal acantholysis with IgG and C3 intercellular deposits on direct immunofluorescence, leading to the diagnosis of localized pemphigus vulgaris. Resolution of the lesions without relapse occurred after low doses of oral prednisone and intralesional triamcinolone acetonide.

Talquetamab-Induced Grover's Disease.

Kresch M, Guénin S, Mubasher A, et al. Talquetamab-induced Grover’s disease. J Drugs Dermatol. 2023;22(8):828-829. doi:10.36849/JDD.7170.

Disseminated papular variant of Dowling-Degos disease: Histopathological features in POGLUT1 mutation.

Dowling-Degos disease is a rare benign genodermatosis. It is characterized by lentiginous hyperpigmentation and reddish-brown papules and plaques. The flexor sides and intertrigines are often affected, but the clinical appearance may vary. Mutations in different genes are responsible for the clinical manifestation. While mutations in the keratin 5 (KRT5) gene favor a reticular distribution pattern, mutations in the POGLUT1 gene lead to a disseminated, papular clinical picture. Acantholytic variants of Dowling-Degos disease have historically been referred to as Galli-Galli disease, but our case study shows that the histopathological changes can vary even within a single patient. To date, no standardized therapy concept exists. The main focus is on keratolytic measures, with varying response. New therapeutic approaches using laser technology appear to be a promising treatment option.

Cutaneous acantholytic dyskeratotic acanthoma accompanying syringofibroadenomatous hyperplasia with proliferation of mature sebocytes: A case report.

Acantholytic dyskeratotic acanthoma is a rare variant of epidermal acanthoma. It has a flat, plaque-like structure and is characterized microscopically by acantholysis and dyskeratosis. Eccrine syringofibroadenomatous hyperplasia is benign and likely reactive. It has recently been considered as a hyperplastic process affecting the eccrine ducts rather than the neoplasm because of its pathological heterogeneity and wide clinical associations. In this article, we present the case of 97-year-old Japanese women with a 10-mm wide, painful acantholytic dyskeratotic acanthoma accompanied by syringofibroadenomatous hyperplasia in the right femoral region. Although syringofibroadenomatous hyperplasia is known to occur as a reactive process with various dermatoses and cutaneous tumors, to date, there have been no reports of cases of acantholytic dyskeratotic acanthoma accompanying syringofibroadenomatous hyperplasia. Moreover, this case also includes the unusual finding of an increase in the mature sebocytes in the area of the syringofibroadenomatous hyperplasia.

Acantholytic dyskeratosis of the vulva presenting with clinical features of vulval lichen sclerosus-A possible rare collision entity.

We present a challenging case of chronic, erosive, scarring dermatosis of the vulva with clinical features of long standing lichen sclerosus (LS), namely pallor and loss of vulval architecture, but with histopathology consistently showing features of an acantholytic process. The history and clinical features of this case do not resemble other acantholytic conditions such as pemphigus vulgaris, Hailey-Hailey disease, Darier disease, or the entities described as acantholytic dermatoses affecting the vulva. As far as we are aware, the combination of the clinical features and histopathologic findings in our case do not fit with any previously described condition and we propose that this is a rare entity of a collision of LS and an erosive acantholytic process occurring together.

Incidental Acantholysis in Hailey-Hailey Disease (Microscopic Nikolsky Sign): An Underappreciated Histologic Sign.

Identification of subtle disease-specific histologic changes may be of significant help in early diagnosis of acantholytic skin diseases. Hailey-Hailey disease (HHD) is an autosomal dominant genodermatosis characterized by vesiculoerosive lesions favoring the intertriginous areas. Histologically, HHD is characterized by full-thickness acantholysis of the spinous layer in association with dyskeratosis of individual keratinocytes; a pemphigus vulgaris-like suprabasal pattern of acantholysis may be observed in the earliest stages of disease. HHD is characterized by highly variable expressivity regarding the age at onset and severity of the disease. Patients may present with late-onset and/or only mild disease. We report the recurrent presence of incidental foci of variably extensive, subclinical acantholysis in multiple bioptic specimens taken from a patient with known HHD for dermatologic conditions other than HHD. Such histologic finding has gone underappreciated in the literature, despite being a likely frequent occurrence in skin biopsies from HHD patients; recognition of this finding might represent a valuable diagnostic clue in selected cases of HHD.

Grover Disease Associated With Chemotherapy: Review of Potential Pathophysiology, Current Treatments, and Future Directions.

INTRODUCTION: Transient acantholytic dermatosis has been frequently reported in patients with malignancies. While paraneoplastic cases have rarely been reported, most eruptions occur in the setting of chemotherapeutic agents. Management is based on limited data and primarily with topical steroids and topical emollients. A subset of patients exhibits recalcitrant disease and require alternate therapeutic approachesMethods: This systematic review consisted of identifying records in PubMed using the medical subject headings (MeSH) terms “chemotherapy” AND “Grover”, “chemotherapy” AND “Grover’s”, “cancer” AND “Grover”, “cancer” AND “Grover’s”, “malignancy” AND “Grover”, “malignancy” AND “Grover’s”, as well as a free text search for “Grover” OR “Grover’s” OR “Grover disease” OR “Grovers disease” OR “Grover’s disease” OR “transient acantholytic dermatosis” OR “transient acantholytic” to identify case reports, case series, systematic reviews, review articles, meta-analyses, clinical trials, brief commentaries, and original articles. The titles and abstracts of all results were reviewed. Full texts of relevant results were then read in their entirety and applicability was determined. RESULTS: Overall, Grover disease has rarely been reported in the setting of malignancy. When it occurs, it is generally in the setting of chemotherapy use. Chemotherapy-associated Grover disease is reported most frequently in association with cytotoxic chemotherapies, followed by small molecule inhibitors. The first line treatment for this complication is the use of topical agents. When these provide inadequate relief, alternate therapies have been rarely reported, with novel treatments proposed based on the type of chemotherapy agent and its mechanism of action. CONCLUSIONS: Chemotherapy-associated Grover disease is an uncommon complication of cancer treatment. While most cases of chemotherapy-associated Grover disease can be treated with topical steroids and topical emollients, certain cases require a more specialized approach. This could include adjuvant adjuvant therapies, or novel treatments that are directly related to the mechanism of action of the chemotherapy involved. J Drugs Dermatol. 2020;19(11):1056-1064. doi:10.36849/JDD.2020.5648.

Gluteal hidradenitis suppurativa presenting pemphigus-like findings: case report.

BACKGROUND: Hidradenitis suppurativa is one member of the follicular occlusion triad: acne conglobata, hidradenitis suppurativa, and dissecting cellulitis of the scalp. The presence of acantholysis and desmoglein autoantibodies in hidradenitis suppurativa is rare. CASE PRESENTATION: We report a case of 68-year-old male with a diagnosis of gluteal hidradenitis suppurativa co-presenting pemphigus-like findings including acantholysis and positive desmoglein autoantibodies. CONCLUSION: To our knowledge, comorbidity of gluteal hidradenitis suppurativa and pemphigus-like findings has not been reported before. This case implies a relationship between two different conditions; the follicular occlusion triad and pemphigus, highlighting a potential induction of pemphigus-like lesion by chronic inflammatory process.

[Ultrastructure of epidermocytes in true pemphigus acantholysis]. / Ul'trastruktura épidermotsitov pri istinnoi akantoliticheskoi puzyrchatke.

OBJECTIVE: To investigate the ultrastructure of epidermocytes in skin biopsy specimens, by taking into account an update on the pathomorphogenesis of true pemphigus acantholysis. MATERIAL AND METHODS: Affected skin biopsy specimens from 4 patients with Pemphigus vulgaris (a mixed mucosal-epidermal variant) and from 1 patient with P. foliaceus at the onset of the disease in the absence of therapy were examined by light microscopy of semifine sections and by transmission electron microscopy. RESULTS: Skin biopsy specimens from pemphigus patients from the foci with a positive Nikolsky's sign were characterized by acantholysis and dilated intercellular spaces in the basal and spinous layers of the epidermis in combination with desmosomal hypoplasia and destruction. The reduction in the organelles of mitochondrial protein synthesis, which causes a decrease in the cytoplasm of the perikaryon and especially in the processes of a number of tonofilaments involved in the formation of desmosomes engaged our attention when studying the ultrastructure of epidermocytes. CONCLUSION: A marked reduction in the number and size of desmosomes in P. vulgaris and P. foliaceus starts in the basal layer of the epidermis; however, acanthosis occurs in the suprabasal and spinous layers, respectively. The universal manifestations of pathology of cytoskeletal elements involved in the formation of desmosomes, as well as their underproduction must be considered in the concept of the pathogenesis of true pemphigus acantholysis.

Clinico-Pathological Study of 4 Cases of Pseudoherpetic Grover Disease: The Same as Vesicular Grover Disease.

INTRODUCTION: Grover disease (GD) was described with 4 histopathological patterns, but later wide histopathological studies found additional ones including vesicular GD. From 2014, 2 new patterns, GD with epidermolytic hyperkeratosis and pseudoherpetic GD, have been proposed. OBJECTIVES: The authors present 4 cases of pseudoherpetic GD and review the 6 previously published cases to better characterize this variant clinically and histopathologically. RESULTS: Half of the patients were men. Mean age at diagnosis was 70, 25 years old. All the patients were immunosuppressed, and 75% of them were treated with chemotherapy. Lesions were asymptomatic or itchy papules sometimes crusted and intermingled with isolated vesicles or pustules mostly in the trunk. Skin biopsies showed intraepidermal vesicles filled with plasma (50%) with floating grouped acantholytic cells. No viral inclusions were found, and immunostaining for herpes virus and varicella zoster was negative. DISCUSSION: Vesicular pattern in GD is described exclusively from a histopathological point of view, and it is defined as the presence of an intraepidermal vesicle filled with plasma and with dyskeratotic cells in the upper part of the vesicle. After reviewing all the described cases, pseudoherpetic GD presents the same histopathological features than vesicular GD, but authors paid attention to the presence of grouped acantholytic cells mimicking multinucleated cells of herpes infection. The authors consider that the so-called pseudoherpetic GD is a vesicular GD, where clinical suspicion of varicella raises this differential diagnosis and leads us to check viral nuclear cytopathic changes, and the authors favor the use of vesicular GD in the dermatopathologist report.

Acantholytic dermatosis of the vagina: the diagnostic challenge of acantholytic disease in the genital region.

We report the case of a 24-year-old woman with an 8-month history of deep pelvic pain and postcoital bleeding. Examination revealed desquamation of the vaginal epithelium with tender fissured plaques in the vagina, initially thought to be vaginal intraepithelial neoplasia. Histology showed squamous mucosa with suprabasal acantholysis and hyperkeratosis, and no evidence of viral infection, dysplasia or malignancy. These findings were consistent with acantholytic dermatosis (AD), a rare lesion that resembles Hailey-Hailey and Darier disease histopathologically, but can be distinguished on a clinical basis. Vulval cases of AD are well recognized, but to our knowledge, this is the first reported case involving the vaginal epithelium alone.

[PEMPHIGUS ACANTHOLYTICUS PARANEOPLASTIC: LITERATURE REVIEW AND CASE REPORT].

The article describes the clinical observation of a rare severe dermatosis, paraneoplastic acantholyticus pemphigus, associated with colon cancer with reference to pathogenesis, clinical variations and difficulties of diagnostics of this condition.

Acantholytic Acanthoma of the Eyelid: Unusual Presentation.

Acantholytic acanthoma is a benign epidermal tumor with a truncal predisposition and is not previously reported as an eyelid mass. A 63-year-old man, presented with a history of nodular masses of both his eyelid margin and eyelid surface of 3 years duration. Excision biopsy of lesion of eyelid margin was consistent with dermal nevus. Lesions of the eyelid surface displayed prominent acanthosis, acantholysis, and spongiosis. Variable hyperkeratosis and papillomatosis was also noted. There was absence of cytological atypia or mitoses. The microscopic picture was consistent with acantholytic acanthoma. The presence of extensive acantholysis in the present case excluded incidental focal epidermolytic hyperkeratosis and focal acantholytic dyskeratosis. Acantholytic vesiculobullous disorders and numerous acanthotic disorders, which are more common in the eyelid, need exclusion. To the authors' best knowledge, as acantholytic acanthoma of the eyelid is not previously reported, they recommend that it should be included as differential diagnoses of benign epidermal lesions of eyelid.

Bullous melanoma: a rare variant of melanoma causing practical problems in determination of tumor thickness.

Bullous melanoma represents a rare variant of melanoma characterized by variably large subepidermal, basilar, or suprabasilar blisters. We present 7 cases of bullous melanoma (M:F = 4:3; median age, 57 years; age range, 38-86) located on the heel (n = 2), foot (n = 2), arm (n = 2), and back (n = 1). In 5/7 cases, the bulla was due to dyscohesiveness of basilar or suprabasilar melanocytes with subsequent acantholytic features simulating pemphigus vulgaris or Hailey-Hailey disease, whereas in the last 2 cases a subepidermal bulla without clear-cut relation to the melanocytic complexes was observed. Direct and indirect immunfluorescence studies performed in 4 patients on skin near the original surgical scar (including those with subepidermal bullae) were negative. Measurement of the Breslow index in all 7 cases was affected by the presence of the bulla, and in 5 of them, the TNM classification was different depending on the method of measurement (with or without the bulla). We suggest that the Breslow index in these cases should be measured detracting the thickness of the bulla from the total thickness, but follow-up data on larger numbers of patients are necessary to establish whether the presence of bullous features has any prognostic implication.

Acantholytic dermatosis of the vulva.

Acantholytic dermatosis of the vulva is a rare condition, presenting with papular eruption in the genital area without history of Darier disease or Hailey-Hailey disease. We report a case with a papular pruritic eruption in the region of the vulva, coalescing into plaques. Biopsy specimen showed irregular acanthosis with an area of split-like bullous formation in the deeper part of the epidermis, as well as acantholytic cells, marked hypergranulosis and hyperkeratosis, compatible with the rare diagnosis of acantholytic dermatosis of the vulva. We review the clinical and histological characteristics of this uncommon disease.

Darier disease: Histopathology revisited.

ABSTRACT: Darier disease (DD) is a rare genodermatosis. Literature on this topic is overwhelmingly dominated by case reports with rare clinical presentations, which have mentioned the histopathologic features briefly. The aim of this study was to document the histopathology of DD. Skin biopsies diagnosed as Darier disease based on clinicopathologic correlation over 12 years were reviewed for various epidermal and dermal features. There were 16 patients included, who most commonly presented in the third decade, with slight female predilection. The most common clinical presentation was hyperpigmented, hyperkeratotic, papules and plaques (91%), with 69% affecting the trunk. In addition to the classic suprabasal acantholytic clefts, we noted some unusual features: absence of parakeratosis (19%), a cornoid lamella-like pattern (62%), follicular acantholysis (13%) and multiple foci of involvement within a single biopsy (63%). Features such as the presence of dyskeratotic cells and minimal dermal lymphocytic infiltrates were concordant with previous literature. The limitation of this study was the small sample size. To conclude, pathologists must be aware of the variations in histopathology of Darier's disease, especially when challenged with atypical clinical presentations. The Darier-like pattern is met within several acantholytic diseases, and clinicopathologic correlation has the last word in arriving at a diagnosis.

Is Grover's disease an autoimmune dermatosis?

Grover's disease (GD) is a transient or persistent, monomorphous, papulovesicular, asymptomatic or pruritic eruption classified as non-familial acantholytic disorder. Contribution of autoimmune mechanisms to GD pathogenesis remains controversial. The purpose of this study was to investigate antibody-mediated autoimmunity in 11 patients with GD, 4 of which were positive for IgA and/or IgG antikeratinocyte antibodies by indirect immunofluorescence. We used the most sensitive proteomic technique for an unbiased analysis of IgA- and IgG-autoantibody reactivities. Multiplex analysis of autoantibody responses revealed autoreactivity of all 11 GD patients with cellular proteins involved in the signal transduction events regulating cell development, activation, growth, death, adhesion and motility. Semiquantitative fluorescence analysis of cultured keratinocytes pretreated with sera from each patient demonstrated decreased intensity of staining for desmoglein 1 and/or 3 and PCNA, whereas 4 of 10 GD sera induced BAD expression, indicating that binding of autoantibodies to keratinocytes alters expression/function of their adhesion molecules and activates apoptosis. We also tested the ability of GD sera to induce visible alterations of keratinocyte shape and motility in vitro but found no specific changes. Thus, our results demonstrated that humoral autoimmunity in GD can be mediated by both IgA and IgG autoantibodies. At this point, however, it is impossible to conclude whether these autoantibodies cause or are caused by the disease. Antidesmoglein antibodies may be triggered by exposure to immune system of sequestered antigens due to disintegration of desmosomes during primary acantholysis. Clarifying aetiology of GD will help improve treatment, which currently is symptomatic and of marginal effectiveness.