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Darier disease (DD) is a rare autosomal dominant keratinizing disorder often characterized by brown scaly pruritic papules over the face, neck, and trunk. Herein is reported a patient who developed secondary cutaneous herpes simplex virus (HSV) following exacerbation of his DD as a result of radiation therapy. In November 2020, a 78-year-old man presented to clinic for a pruritic rash on his back consistent with DD. He had developed the rash after the conclusion of chemoradiation therapy for recently diagnosed urothelial carcinoma of the bladder with squamous differentiation. However, he returned two weeks later complaining of a marked worsening of the rash associated with a pain and burning sensations. Histopathology was non-conclusive, but the lesions were found to be positive for HSV-1 by PCR. The patient recovered without complication over a period of two weeks following a course of valacyclovir. There is precedent in the literature for ionizing radiation inducing flares of DD lesions in overlying skin. In addition, DD has been shown to put a patient at increased risk for secondary infections such as HSV. This case report demonstrates that HSV could pose a significant risk to those with DD receiving radiation therapy and thus could warrant prophylactic treatment.

The location of the patient's lesions, as well as her underlying conditions, pointed to the diagnosis.

Darier disease is considered a hereditary acantholytic dermatosis that is inherited in an autosomal dominant manner and usually manifests in the first or second decade of life. We describe a 62-year-old man with an acquired variant of Darier disease after a recent diagnosis of metastatic prostate cancer. We discuss and postulate a novel mechanism for this unusual presentation.

Keratosis pilaris is a common skin disorder comprising less common variants and rare subtypes, including keratosis pilaris rubra, erythromelanosis follicularis faciei et colli, and the spectrum of keratosis pilaris atrophicans. Data, and critical analysis of existing data, are lacking, so the etiologies, pathogeneses, disease associations, and treatments of these clinical entities are poorly understood. The present article aims to fill this knowledge gap by reviewing literature in the PubMed, EMBASE, and CINAHL databases and providing a comprehensive, analytical summary of the clinical characteristics and pathophysiology of keratosis pilaris and its subtypes through the lens of disease associations, genetics, and pharmacologic etiologies. Histopathologic, genomic, and epidemiologic evidence points to keratosis pilaris as a primary disorder of the pilosebaceous unit as a result of inherited mutations or acquired disruptions in various biomolecular pathways. Recent data highlight aberrant Ras signaling as an important contributor to the pathophysiology of keratosis pilaris and its subtypes. We also evaluate data on treatments for keratosis pilaris and its subtypes, including topical, systemic, and energy-based therapies. The effectiveness of various types of lasers in treating keratosis pilaris and its subtypes deserves wider recognition.

Darier disease is an autosomal-dominant inherited condition caused by mutation of a gene, which produces a protein involved in calcium channel regulation. The disease has a variety of manifestations and lacks consistent genotype-phenotype correlations. Acral hemorrhagic Darier disease causes macules, papules, vesicles and/or hemorrhagic blisters on the extremities. Other classic signs of the disease may be present in the same patient or relatives. Histopathology reveals dyskeratosis and suprabasal acantholysis with hemorrhagic lacunae. We report 3 new cases of this type of Darier disease triggered by injuries. Response to retinoid therapy was good., (Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Kyrle's disease is a rare skin disorder which is characterized by hyperkeratotic papules and nodules with a central keratotic plug mostly located in lower limbs. Exact etiology of Kyrle's disease is unknown, but its association has been reported sparsely with renal disorders, uremic patients on dialysis, diabetes mellitus, liver disease and paraneoplastic syndromes, tuberculosis and some fungal diseases. We report Kyrle's disease in a middle aged female suffering from diabetes mellitus with diabetic nephropathy on hemodialysis., (© Journal of the Association of Physicians of India 2011.)

We report two cases of biopsy-confirmed Kyrle disease. Kyrle disease is one of the perforating dermatoses associated with diabetic patients undergoing renal dialysis. In this report, we describe the clinical and histopathologic features, the differential diagnoses, and successful treatment of this unusual disorder.

Importance: Keratosis pilaris and keratosis pilaris-like eruptions have been reported in association with RAF inhibitors sorafenib and vemurafenib. We describe herein what is to our knowledge the first reported case of new onset keratosis pilaris after discontinuation of EGFR inhibitor erlotinib., Observations: A 60 year-old female with stage IV lung cancer was treated with erlotinib (100 mg/d). The patient elected to discontinue erlotinib after four years secondary to adverse systemic reactions. However, five months later small, monomorphic, rough, folliculocentric papules with surrounding mild erythema characteristic of keratosis pilaris were noted on upper back and arms., Conclusions and Relevance: This serves as the first documented case of new onset keratosis pilaris in a patient after discontinuation of erlotinib. We report the present case to show the possible association of keratosis pilaris with not only RAF inhibitors, but also the EGFR inhibitor erlotinib. Further investigation will determine whether this is a class effect with other systemic EGFR inhibitors.

Background: Ulerythema ophryogenes (also known as keratosis pilaris atrophicans faciei) is a rarely reported cutaneous manifestation of Noonan syndrome., Objective: Recognizing ulerythema ophryogenes as a cutaneous association in Noonan syndrome may aid in the diagnosis of this relatively common genetic condition., Methods: We present a case of a patient with Noonan syndrome and ulerythema ophryogenes associated with a SOS1 mutation and review the literature on this association., Results: To the best of our knowledge, this is the second case of Noonan syndrome proven to be due to an SOS1 mutation in which ulerythema ophryogenes was clinically recognized and specifically diagnosed., Conclusions: The presence of ulerythema ophryogenes in a patient with Noonan syndrome increases the likelihood of a SOS1 mutation. Further reports by dermatologists and medical geneticists documenting ulerythema ophryogenes and not just descriptions of sparse or absent eyebrows will help support this genotype-phenotype correlation.

Keratosis follicularis squamosa (KFS) is a keratinizing disorder that is characterized by asymptomatic small scaly patches with follicular plugs scattered on the trunk and thighs. Irritation by clothing, bacterial infections, heredity and hormone imbalances have all been proposed as pathogenic factors. Case 1 involved an 11-year-old Japanese female who presented with a 1-year history of small patches on the lateral chest. She had been attending swimming classes for seven years. A histological examination showed dilated hair follicles with keratotic plugs. A bacterial culture of the lesion detected Staphylococcus auricularis. Case 2 involved a 5-year-old Japanese female who presented with a 1-year history of eruptions on the lateral trunk. The eruptions appeared after she began to attend swimming classes. The physical and histological findings of Case 2 were similar to those of Case 1. A bacterial culture test detected Staphylococcus capitis. Both cases were diagnosed as KFS. The patient in Case 1 changed her swimsuit and was treated with 50 mg of oral minocycline daily. The patient in Case 2 stopped attending swimming classes without receiving any treatment. The skin lesions in both cases completely disappeared within a few months. The clinical courses of these patients suggest that swimsuit friction was the cause of KFS.

Segmental Darier's disease is a rare clinical variant of autosomal dominant Darier's disease (keratosis follicularis) exhibiting eruptions in a unilateral arrangement following the lines of Blaschko. It occurs in approximately 10% of patients with Darier's disease. We report two cases of type 1 segmental Darier's disease that appeared a few months after childbirth; in one case, recurrence of the disease occurred after tubal ligation.

We herein report a sporadic case of Darier's disease localized to the bilateral side of the neck in a 39-year-old Japanese woman. Several clinical variants of Darier's disease have so far been recognized including unilateral Darier's disease, localized Darier's disease, segmental Darier's disease and acral Darier's disease. Few cases of Darier's disease, restricted to sun-exposed areas such as the bilateral side of the neck, have been described in the published work. It remains controversial, however, whether ultraviolet exposure can induce the onset of Darier's disease. Our patient's skin lesions, which were resistant to previous treatment with corticosteroid, improved substantially with high-concentration tacalcitol lotion and sunscreen. This is the first report on the efficacy of topical tacalcitol lotion associated with sunscreen for the treatment of localized Darier's disease.

The ATP2A2 gene encodes Ca2+-dependent ATPase, the dysfunction of which causes Darier disease. In this study, we analyzed the promoter structure of the human ATP2A2 gene using primary normal human keratinocytes (NHK). Reporter assays showed that deletion of -550/-529, -488/-472, -390/-362, or -42/-21 resulted in a significant decrease in human ATP2A2 promoter activity. Electrophoretic mobility shift assay (EMSA) showed that Sp1 is a transcription factor that binds to the -550/-529 and -488/-472 regions of the promoter. Chromatin immunoprecipitation (ChIP) assay demonstrated that Sp1, but not Sp3, binds to the promoter region of the ATP2A2 gene in NHK cells in vivo. Knockdown of Sp1 expression by small interfering RNA resulted in a marked reduction in ATP2A2 promoter activity and ATP2A2 mRNA levels in NHK, suggesting that Sp1 positively transactivates the ATP2A2 promoter in NHK. This is early evidence demonstrating that Sp1 plays an important and positive role in ATP2A2 gene expression in NHK in vivo and in vitro.

Phrynoderma is a distinctive form of follicular hyperkeratosis associated with nutritional deficiency. Although originally thought to represent vitamin A deficiency, several studies have demonstrated multiple etiologies. Characteristic skin lesions are hyperkeratotic papules that first appear on the extensor surfaces of the extremities, shoulders, and buttocks. We report a 14-month-old boy with malnourishment and hyperkeratotic papules and plaques with histologic changes typical of phrynoderma. Despite an extensive evaluation, a specific nutritional deficiency was not identified. Phrynoderma is believed to be a manifestation of severe malnutrition, not necessarily accompanying low vitamin A levels. While the literature supports a link between phrynoderma and vitamins E, B, A, and essential fatty acids general malnutrition seems to be the strongest association. The clinical picture typically improves with enhanced nutritional status. Phrynoderma must be considered in the differential diagnosis in patients with extensor surface hyperkeratotic papules and plaques in the setting of malnourishment and should prompt the clinician to evaluate cell markers of nutritional status, not just vitamin A. We believe this patient exemplifies the conundrum that faces clinicians in evaluating patients with extensor surface predominant hyperkeratotic papules and plaques in the setting of malnourishment.

Inverted follicular keratosis is characterized by a squamous epithelial expansion of the infundibular portion of the hair follicle in an exophytic and endophytic pattern. The lesion is often associated with squamous eddies similar to an irritated keratosis and may have a superficial papillomatous architecture. The lesion most often arises as a solitary nodule on the face of middle age to elderly individuals. Inverted follicular keratosis has been described as a distinct entity by some while others believe that it is related to trichilemmomas and/or verruca vulgares. The cutaneous pathology of Cowden's syndrome is characterized by multiple trichilemmomas. We present a woman who fulfills the clinical criteria for Cowden's syndrome and who initially presented with multiple inverted follicular keratoses. Also, in situ hybridization studies performed on the patient's keratoses do not reveal evidence of human papillomavirus infection.

We report a sporadic case of Darier's disease restricted to sun-exposed areas in a 17-year-old Japanese girl. There are several clinical variants of Darier's disease including unilateral Darier's disease, localized Darier's disease, segmental Darier's disease, and acral Darier's disease, but few cases of Darier's disease restricted to sun-exposed areas have been described in the literature. Although it remains controversial whether UV irradiation can evoke the eruption of Darier's disease or not, cases of Darier's disease restricted to sun-exposed areas like our case may help to further clarify the relationship between Darier's disease, UV irradiation and photo-exacerbation of this autosomal dominant genodermatosis.

Darier's disease is an autosomal dominant disease that typically arises during the first or second decades of life. It involves the abnormal keratinization of the epidermis, mucosa, and nails. We describe a 74-year-old man with metastatic carcinoma in whom fibroproliferative disease and an acquired variant of Darier's disease developed, both of which may have been paraneoplastic processes.

An increased incidence of scabies has been noted in many countries. Difficulties may arise when unrecognized infestations trigger or aggravate other dermatological disorders. We present an instructive case of Darier's disease, which did not respond to appropriate therapy regimens due to constant triggering by an undetected underlying scabies infestation. In this case, a 44-year-old Italian man presented with typical symptoms of Darier's disease. In addition, the patient reported massive pruritus, which is rather uncommon in this disorder. The disease proved recalcitrant to established treatment regimens resulting in excessive treatment costs. We confirmed the diagnosis of Darier's disease by histopathological analysis, and, in addition, detected arthropod fragments in the upper epidermis. Systemic ivermectin and topical allethrin followed by acitretin and PUVA-bath therapy resulted in rapid improvement of the debilitating pruritus as well as alleviation of the symptoms of Darier's disease.

In skin, desmosomes constitute critical adhesion complexes between adjacent keratinocytes that help maintain an intact epidermis. However, individual keratinocytes need to migrate and differentiate and therefore desmosomes must have an inherent dynamic capacity to assemble and disassemble. This review highlights the role of the different structural junctional components involved in desmosome formation and turnover, as well as the possible signalling processes and pathways that may be implicated in desmosome homeostasis. Clues to the intricate nature of desmosome assembly and disassembly have been derived from human inherited and acquired blistering skin diseases as well as animal models and basic cell biology studies. The key implications for understanding desmosome dynamics from these findings are summarized in this review.

Darier's disease, keratosis follicularis, is frequently aggravated by sun exposure. Although there have been reports of Darier's disease reproduced by repeated exposure to ultraviolet B, little is known about its photo-protection. We artificially induced Darier's disease in a 47-year-old Korean man, and tested the protection afforded by sunscreen and topical ascorbic acid. Complete lesions of Darier's disease arose with repeated exposure of ultraviolet B (2,600 mJ/cm2 for 10 days), and sunscreen and topical ascorbic acid protected against its appearance. This result strongly suggests that sunscreen and ascorbic acid would be very helpful in preventing the aggravation of Darier's disease caused by sun exposure.

We investigated a radiotherapy-induced flare and subsequent clearance of skin lesions of a patient with the rare, dominantly inherited genodermatosis, Darier's disease (DD). The DD gene, ATP2A2, was recently isolated and shown to be a cation pump responsible for regulating intracellular calcium homeostasis. A severe exacerbation of Darier's skin lesions developed within the radiation field when 40 Gy of palliative thoracic external-beam radiation therapy and concurrent chemotherapy (cisplatin and hydroxyurea) were delivered for non-small cell lung cancer. The DD lesions subsequently completely cleared from irradiated skin, as they did when a subsequent course of radiation alone was given for a loco-regional tumor recurrence. The two radiation therapy-treated areas of skin remained free from lesions of the skin disorder until the patient's death from progressive lung cancer 9 months later. The nucleotide sequence of the patient's ATP2A2 gene was determined by PCR-based cycle sequencing. We identified four nucleotide sequence variants in the ATP2A2 gene in this patient. Three were probable polymorphisms and the other appeared to be a novel disease-causing mutation (R751Q), situated in the transmembrane portion of the ATP2A2 protein. This finding confirmed the clinical diagnosis. Since epidermis turns over every 3-4 weeks, total and persistent clearance of the DD lesions by chemoradiotherapy suggests that this treatment induced sustained differentiation of the DD-affected skin by an unknown mechanism. Oncologists treating malignant disease in patients with DD should anticipate temporary deterioration in DD-involved irradiated skin. Radiation therapy has therapeutic potential in severe DD.

We report a case of acantholytic dyskeratotic epidermal nevus induced by repeated ultraviolet B radiation in a 16-year-old Korean girl. She had experienced pruritic skin rashes on the right side of the abdomen and flank area in a zosteriform distribution for the past 10 years. They were aggravated during the summer and spontaneously disappeared in the winter. Papules revealed acantholytic dyskeratotic cells that were diagnosed as acantholytic dyskeratotic epidermal nevus. Suberythemal and erythemal doses of UVB were irradiated to the lesional skin (right side of abdomen) and nonlesional skin (left side of abdomen) for 4 consecutive days. UVB-induced pruritic papules were observed on the lesional skin and a biopsy specimen of the papules also showed acantholytic dyskeratotic cells, which were compatible with acantholytic dyskeratotic epidermal nevus.

Combination UVA/UVB radiation and UVB radiation alone have been shown to induce the lesions of Darier-White disease. However, 6% of patients with Darier-White disease claim that sunlight ameliorates their condition. We performed an unblinded, side-by-side controlled trial of UVB, UVA, and combination UVB/UVA phototherapy in a patient with historically photoameliorated Darier-White disease to determine whether phototherapy was beneficial, to determine whether phototherapy-related heat was detrimental, and to confirm, with appropriate controls, the action spectrum of the disease. Phototherapy with radiation in the UVB but not UVA spectrum evoked Darier-White disease in this patient, both clinically and histologically. UVB radiation was capable of inducing Darier-White disease in vivo in spite of a history of photoamelioration, whereas UVA radiation alone and the heat associated with phototherapy in our protocol had no effect on the disease.

We describe two patients with painful follicular keratoses at lower limb amputation sites. Subsequent examination of 31 amputees revealed evidence of keratoses in four of 28 patients with lower limb stumps. Two of the four affected subjects experienced stump pain exacerbated by weight-bearing. This problem is not well documented. Local treatment measures may be ineffective. Painful stump follicular keratoses may be a cause of significant morbidity in lower limb amputees, and may be the result of an ill-fitting prosthesis.

Introduction: Occurrence of localized Darier's disease was discussed. We report one case of photo-induced and localized Darier., Case Report: Our patient had had a linear eruption every summer for ten years. Clinical and photological examinations showed an acantholytic dyskeratosis as well as Darier's disease. Lesions were reproduced during photobiological examinations by UVB phototests., Discussion: Several diagnoses could have been considered: Darier's disease or acantholytic dyskeratosis dermatosis as Grover's disease or Hailey-Hailey's disease or acantholytic dyskeratosis nevus. Clinical features and linear eruption following Blaschko's lines pleads for cutaneous mosaicism of Darier's disease. Photobiological explorations and literature data shows that UVB photo-induced lesions are different from isomorphic response of Koebner after irritant application.

We report a case of scurvy. This case is interesting by the unilateral character of the ecchymotic leg's purpura. Ascorbic acid assays do not yet enable subclinical vitamin C deficiency to be reliably detected. Hence the importance of knowing the situation which expose to this deficiency.

We report two cases of mycosis fungoides with marked, pleomorphic follicular manifestations. Follicular hyperkeratosis, comedo-like lesions, acquired epidermal cysts, and patchy alopecia developed in various locations in both patients. Findings of histopathologic and immunohistochemical studies showed atypical CD4+ T lymphocytes infiltrating the follicles without follicular mucinosis. Focal expression of intercellular adhesion molecule type 1 was observed within the cyst walls. These findings suggest that the follicular lesions were specific for mycosis fungoides. These manifestations represent a distinct clinical and histologic form of mycosis fungoides. This variant probably accounts for cases of mycosis fungoides with clinically suspected alopecia mucinosa in which follicular mucinosis cannot be histologically proved.

A 48-year-old man, in a chronic hemodialysis program, had numerous skin lesions develop that consisted of follicular papules and small hyperkeratotic nodules, located on the trunk, hips, and upper and lower extremities (where the lesions were more numerous). The nodules measured 3 to 5 mm and had a dark discoloration (Figs 1 and 2). Four months previously, the patient noticed the appearance of disseminated papular and pruritic lesions. The lesions did not improve with the prescribed local nonspecific treatment. The patient had chronic renal failure during the previous 10 years, secondary to renal vein thrombosis. As a result, he has had periodic hemodialysis for 18 months. The clinical diagnosis of the skin lesion was Kyrle disease, and a skin biopsy was performed on a nodular lesion from the thigh. The histologic sections showed skin with hyperkeratosis, an invagination of the epithelium filled with keratin and amorphous material. In some sections, the invagination appeared to be a cyst, which in serial sections, showed partial rupture of the lateral wall. No evidence of hair was found inside the invagination.

The cutaneous signs of diabetes have been reviewed in the past. This review shpeds new light on old associations. Some skin signs of diabetes are questioned and additional cutaneous manifestations of diabetes are described herein.

RNA and protein synthesis of dyskeratotic cells in Darier's disease was studied by autoradiography after in vitro incubation with 3H-uridine, 3H-leucine and 3H-histidine. These three isotopes were incorporated in cells constituting the basis and wall of the lacuna, while they did not accumulate in isolated acantholytic and dyskeratotic cells in the lacuna, corps ronds and grains.