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.

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.

Anti-desmoglein 1 antibody-positive mother and antibody-negative child with Darier's disease.

We report a mother and an adult son with Darier's disease. The mother, 76 years old and Japanese, had positivity for anti-desmoglein (Dsg)1 antibodies. She had erythema with hyperkeratosis and seborrheic and interstitial blistering. A high level of anti-Dsg1 antibodies was detected in the serum. Histopathological examination showed acantholysis and direct immunofluorescence testing revealed intercellular IgG and C3 deposition of the epidermis. Although she was diagnosed as having pemphigus foliaceus, the skin lesions slightly improved with immunosuppressive therapy. Her son, 47 years old, had similar skin lesions on the seborrheic and interstitial parts, but the anti-Dsg1 antibodies were negative in his serum. Histopathological examination showed acantholysis and dyskeratotic cells. Although Hailey-Hailey disease was first suspected, no mutation in the ATP2C1 was detected in either patient. Trio-exome analysis including the father showed a heterozygous c.2027C>A transition on exon 14 of ATP2A2, causing a replacement at amino acid 676 (p.Ala676Asp) in the mother and son only. The two patients were then diagnosed as having Darier's disease. Exome analysis further showed that a novel heterozygous missense mutation of DSG1 was identified only in the affected mother. Anti-Dsg1 antibody-positive Darier's disease is reported here for the first time. Very rare coexistence of Darier's disease and anti-Dsg1 antibody-positivity might be associated with this novel heterozygous DSG1 mutation. Experimental evidence is required to validate this hypothesis.

Drug-induced Grover's disease: a case report and review of the literature.

BACKGROUND: Grover's disease (GD) is a relatively rare transient dermatosis that can be idiopathic or acquired. Acquired GD may occur secondary to internal triggers such as medications and malignancies and external factors such as friction. OBJECTIVE: The purpose of this report is to describe the clinical and histological presentation of drug-induced Grover's disease (DIGD) and discuss potential pathogenic mechanisms. METHODS: A systemic review of the literature was performed to identify medications implicated in DIGD. RESULTS: We identified 13 reports of patients with DIGD. Most patients presented with a papular or papulovesicular morphology involving the trunk and extremities. Pruritus was the most common symptom. The majority of the offending agents were cancer therapeutics. Discontinuation of the culprit medication was sufficient for rash clearance and symptom resolution in most cases. CONCLUSION: The overlap in morphology and associated symptoms in DIGD and GD makes the diagnosis of DIGD challenging and has potentially led to underdiagnosis. However, in cases of more extensive involvement and treatment recalcitrance, a drug-induced eruption should be considered.

Case for diagnosis. Atypical Grover's disease

Abstract A 55-year-old male presented with an eight-month history of erythematous papules and plaques with demarcated areas of spared skin on his trunk, upper extremities, neck, and face. Grover's disease is a rare, acquired disorder of unknown origin, which is classically characterized by the appearance of erythematous papules on the upper trunk that are usually transient. As in the present case, there are reports of atypical disease, with facial involvement, pityriasis rubra pilaris-like lesions, and a more chronic course.

Dowling-Degos disease: a review.

Dowling-Degos disease is a rare autosomal dominant genodermatosis. It is characterized by acquired reticulate hyperpigmentation over the flexures, comedone-like follicular papules, and pitted perioral scars that usually develop during adulthood. Mutations in genes affecting melanosome transfer, and melanocyte and keratinocyte differentiation have been implicated in the pathogenesis of this disease. These genes include KRT5, POFUT1, POGLUT1 and, most recently, PSENEN. Dowling-Degos disease can be found in isolation or with other associated findings, most notably hidradenitis suppurativa. This condition belongs to a spectrum of conditions that all result in reticulate hyperpigmentation that at times are hard to distinguish from each other. The most closely linked entity is Galli-Galli, which is clinically indistinguishable from Dowling-Degos disease and can only be distinguished by the presence of acantholysis on microscopy. Unfortunately, Dowling-Degos disease is generally progressive and recalcitrant to treatment.

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.

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.

A rare acantholytic variant of squamous cell carcinoma of the maxilla: A case report and literature review.

RATIONALE: Acantholytic squamous cell carcinoma (ASCC) is an uncommon histopathologic variant of squamous cell carcinoma (SCC), which is the most common malignancy of the oral cavity. Though ASCC showed poor prognosis, the exact diagnosis is challenging. PATIENTS CONCERNS: A 59-year-old female patient with 1-month long symptoms of pain and burning sensation in the right maxilla. DIAGNOSES: Incisional biopsy in the maxilla established the pathologic diagnosis of SCC. INTERVENTION: The patient underwent mass resection with near total maxillectomy. OUTCOMES: The final diagnosis through the microscopic examination was ASCC. Palliative chemotherapy was done to relive the symptoms after the recurrence, however, the patient died of the disease at 8 months after her initial presentation. LESSONS: Special attention should be paid to this variant of SCC because most patients with ASCC have a very poor prognosis.

Grover disease: review of subtypes with a focus on management options.

Grover disease (GD) is a benign eruption that causes a papulovesicular rash on the trunk and proximal extremities. It often resolves spontaneously but can follow a more chronic and fluctuating course that may last several years. Although the etiology remains unknown, several associated triggers have been identified including heat and sweating, cool and dry air, renal failure, malignancy, and the initiation of several drugs. Since the disease tends to resolve on its own, management is aimed at disease prevention and symptomatic relief. First-line therapy includes topical steroids and vitamin D analogues with adjuvant antihistamines. In more severe cases that are refractory to less aggressive therapy, systemic corticosteroids, retinoids, and phototherapy may lead to successful resolution. Novel therapies are few and have little evidence but involve innovative use of light therapy and immune modulators. Herein, we review the literature and new trends of GD with a focus on established and novel treatments.

Grover's Disease in a Kidney Transplant Recipient.

Dear Editor, It is not unusual for patients with renal insufficiency to develop skin pathologies. There are reports in the literature of increased incidence of calciphylaxis, pruritus, perforating dermatoses, and porphyria cutanea tarda in this patient population (1). Although it is quite rare, Grover's disease (GD) has been reported in several patients with renal insufficiency, but only once in a renal transplant recipient (2). The disease follows three patterns: persistently pruritic, transient eruptive, or a chronic asymptomatic course (3). Common risk factors concomitant with disease prevalence are immunosuppression, HIV, hemodialysis, viral and bacterial infections, malignancies, and other skin pathologies like contact and atopic dermatitis (4). A 60-year-old woman had a family history of polycystic kidney disease and was subsequently diagnosed in 1997. The patient had concomitant hepatic involvement and a stable aneurysm of the anterior cerebral artery. Consequently, the patient preemptively received a kidney transplant in 2015. The immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil, and prednisone with basiliximab induction. In 2017, a biopsy of the right thigh demonstrated squamous cell carcinoma in situ measuring 1×1cm in size. The lesion was treated with surgical excision. The patient also exhibited an erythematous brown macule with undefined borders on the left side of the nose with a size of 12 mm; it was later determined to be actinic keratosis. The lesion was treated successfully with cryotherapy. During this period, a fever prompted a PCR for BK virus DNA which showed a substantial amount of copies, measuring 28,850 copies/mL in urine and 98 copies/mL in blood. The mycophenolate dose was reduced, and tacrolimus trough concentration was maintained at between 3 and 5 µg/L. In 2018 the patient presented with multiple pruritic erythematous papules located on the trunk. Upon histological biopsy, there was dominant suprabasal acantholysis with numerous cells separating from the epithelium. Furthermore, there was a moderate amount of mononuclear infiltrate in the upper portion of the dermis and sparse suprabasal clefts (Figure 1). Clinical presentation and histologic examination were consistent with Grover's disease. The patient was treated topically with betamethasone cream twice daily for four weeks. The skin changes persisted for only a few weeks. The pathophysiological mechanism causing GD is still unknown. It is usually only a transient skin condition that lasts no more than a few weeks, but there have been more chronic cases lasting for years, particularly in patients on hemodialysis (5). The lesions commonly affect the chest area but may spread to diffusely envelope the body as erythematous papules, pustules, lichenoid lesions, or vesicles (2). Grover characterized 4 different subtypes based on the pathohistological findings as Darier-like (the most common), pemphigus vulgaris-like, Hailey-Hailey-like, or spongiotic subtype (3). The histological patterns are not exclusive to one patient and may even be found concomitantly in a single lesion. The condition is definitively diagnosed through histology, showing distinctive acantholysis along the epidermis with dyskeratosis that is described as "corps ronds" and "grains" (3). Grover's disease is more prevalent in middle-aged Caucasian men than any other group, with a 1.6-2.1 gender ratio (6). It was originally thought that the disease was caused by dysfunctional eccrine sweat glands, as the ailment was more common in patients that had increased perspiration either due to environmental heat, fever, or extensive bedrest. This idea was reinforced by histological evidence of atrophied sweat glands in uremic patients with renal insufficiency (7). Moreover, a case series and case report described remissions of GD in their patients on hemodialysis that received a renal transplant (5,8). However, subsequent studies have not supported an association with sweat dysfunction and disease development, while others have only managed to attribute sweat gland dysfunction as the primary trigger in 20-30% of cases (9). Conversely, cold dry air and xerosis cutis is thought to trigger the disease because it is four times more likely to be diagnosed in the winter months (10). Ultraviolet radiation has been identified as an exacerbating factor for GD, which could have been the trigger for onset of disease in our patient as demonstrated by her squamous cell carcinoma and actinic keratosis (11). Despite immunosuppression being a risk factor for GD, as shown by its association in patients with HIV, bone marrow transplantation, hemodialysis, and hematological malignancies, GD has been reported only once in the literature after a renal transplant (2,4). As our case, that patient developed GD a few years after transplant without an obvious trigger and the lesions appeared as red papules that were disseminated over the anterior thorax. Their patient's cutaneous lesion resolved spontaneously after 2 weeks and never returned in the 2.5-year follow-up period. Their patient has had two renal allografts over a 20 year timespan, while ours had had her graft for only two years. The immunosuppressive regimen was slightly different: cyclosporine, azathioprine, and methylprednisolone versus our combination of tacrolimus, mycophenolate mofetil, and prednisone. Grover's disease can be treated conservatively by avoiding risk factors such as UV light and sweating as well as and applying moisturizing emollients which may cause the lesion to resolve spontaneously. Medical therapy consists of topic corticosteroids, topical vitamin D analogues, oral retinoids, and oral corticosteroids, PUVA, and methotrexate for resistant cases (6,12). When a patient exhibits pruritic papules of the skin, GD should be considered in differential diagnosis, especially in kidney transplant patients and those on hemodialysis. While the condition is rare, increased recognition in this patient population will allow for studies to further characterize this poorly understood disease.

[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.

Enfermedades acantolíticas: caracterización de pacientes con diagnóstico de enfermedad de Hailey-Hailey, enfermedad de Darier y enfermedad de Grover, entre los años 2007 y 2017 en el Hospital Clínico San Borja Arriaran y revisión de la literatura / Characterization of patients diagnosed with Hailey-Hailey disease: Darier's disease and Grover's disease, between 2007 and 2017 at the San Borja Arriaran Clinical Hospital and review of the literature

INTRODUCCIÓN: Las enfermedades acatólicas son un grupo heterogéneo de enfermedades que presentan como característica central histopatológica la acantosis. Generalmente presentan un curso de evolución crónica y recidivante, con variadas manifestaciones clínicas. OBJETIVO: caracterizar los pacientes con diagnóstico de enfermedad acantolítica, bajo 5 criterios clínicos y realizar una revisión de la literatura. MÉTODOS: Se realizó una revisión de la base de datos del Servicio Anatomía Patológica del Hospital San Borja Arriaran (HSBA) entre los años 2007 y 2017 y se complementaron con los antecedentes clínicos extraídos de las fichas clínicas.RESULTADOS: Se obtuvo un total de 13 casos. el 53,8% correspondieron a enfermedad de Darier, 20,6% a enfermedad de Hailey-Hailey y un 20,6% a enfermedad de Grover, obteniendo un promedio de edad al momento del diagnóstico de 22,5 años, 44,3 años y 47,6 años respectivamente. Los antecedentes familiares estuvieron presentes en el 53,8% del total de pacientes, ninguno de ellos presentaba estudio genético. El 61,5% de la muestra correspondió a pacientes de sexo femenino y el promedio de años de evolución previo al diagnóstico fue de 7,4 años para Darier, 8,6 para Hailey-Hailey y para Grover. El 100% de los pacientes con enfermedad de Darier y Grover estaban con terapia sistémica y el 66,6% de enfermedad de Hailey-Hailey con terapia tópica, todos con adecuada respuesta clínica. DISCUSIÓN y conclusiones: las enfermedades acantolíticas corresponden a genodermatosis poco frecuente cuyo diagnóstico y tratamiento constitu-yen un desafío para el dermatólogo

INTRODUCTION: Atytolic diseases are a heterogeneous group of diseases that present acanthosis as a histopathological central characteristic. They usually present a course of chronic and recurrent evolution, with varied clinical manifestations. OBJECTIVE: to characterize the patients diagnosed with acantholytic disease, with 5 clinical criteria and to carry out a review of the literature. METHODS: A review of the database of the Pathological Anatomy Service of the San Bor-ja Arriaran Hospital (HSBA) between 2007 and 2017 was carried out and complemented with the clinical records extracted from the clinical files. RESULTS: A total of 13 cases were obtained. 53.8% corresponded to Darier's disease, 20.6% to Hailey-Hailey's disease and 20.6% to Grover's disease, obtaining an average age at diagnosis of 22.5 years, 44.3 years and 47.6 years respectively. Family history was present in 53.8% of the to-tal patients, none of them had a genetic study. 61.5% of the sample corresponded to female patients and the average of years of evolution prior to diagnosis was 7.4 years for Darier, 8.6 for Hailey-Hailey and for Grover. 100% of the pa-tients with Darier and Grover's disease were on systemic therapy and 66.6% of Hailey-Hailey's disease with topical therapy, all with adequate clinical response. DISCUSSION AND CONCLUSIONS: acantholytic diseases correspond to rare genodermatosis whose diagnosis and treatment constitute a challenge for the dermatologist.