An unusual presentation of extragenital lichen sclerosus-An extensive keratotic variant.

In this case report, we outline a case of a 71-year-old woman who presented to the dermatology clinic with a history of keratotic and atrophic warty-like plaques on her lower limbs, which limited the movements in her right lower extremity. A skin radial biopsy of one of the plaques was performed and the diagnosis of extragenital lichen sclerosus (ELS) was established. She underwent an anogenital exam and fortunately, lesions were not found. The patient in this case showed an unusual variant of ELS.

Use of 5-Alpha Reductase Inhibitors in Dermatology: A Narrative Review.

Finasteride and dutasteride are 5-alpha reductase selective inhibitors (5ARIs). They were introduced as therapeutic agents for the treatment of benign prostatic hyperplasia in 1992 and 2002, respectively; finasteride has also been approved for the treatment of androgenetic alopecia since early 2000. These agents inhibit the conversion of testosterone (T) to 5α-dihydrotestosterone (5α-DHT), limiting steroidogenesis and playing a crucial role in the physiological function of the neuroendocrine system. Therefore, it has been proposed that blocking androgen synthesis with the use of 5ARIs would be beneficial in the treatment of various diseases related to states of hyperandrogenism. This review describes the dermatological pathologies in which 5ARIs have been used as part of the treatment, evaluation of the efficacy, and knowledge of the safety profile. Specifically, we discuss the application of 5ARIs in androgenetic alopecia, acne, frontal fibrosing alopecia, hirsutism, and the implications of adverse events associated with its use to inform about the applications of 5ARIs in general dermatology practice.

Clinical, pathological, and molecular correlation of folliculocystic and collagen hamartoma: A new potential diagnostic criterion for tuberous sclerosis complex?

Folliculocystic and collagen hamartoma (FCCH) is a rare entity with only 18 reported cases worldwide. Of them, most are found in patients diagnosed with tuberous sclerosis complex (TSC). FCCH has distinctive histopathologic features, including collagen deposition in the dermis, perifollicular fibrosis, and comedones with keratin-containing cysts lined by infundibular epithelium. We report three patients with a definitive TSC clinical diagnosis in whom clinical, histopathologic, and molecular features were studied to establish if there exists a genotype-phenotype correlation. The molecular results showed different heterozygous pathogenic variants (PV) in TSC2 in each patient: NM_000548.4:c.5024C>T, NG_005895.1:c.1599+1G>T, and NM_000548.4:c.2297_2298dup, to our knowledge; the latter PV has not been reported in public databases. The same PVs were identified as heterozygous in the tumor tissue samples, none of which yielded evidence of a TSC2 second hit. Because all FCCH patients with available molecular diagnosis carry a pathogenic genotype in TSC1 or TSC2, we suggest that FCCH should be considered as a new and uncommon diagnostic manifestation in the TSC consensus international diagnostic criteria. The early recognition of FCCH by clinicians could prompt the identification of new TSC cases. Interestingly, our molecular findings suggest that one of the patients described herein is a probable case of somatic mosaicism.

Cowden Disease: A Review.

ABSTRACT: PTEN hamartoma tumor syndrome (PTHS) includes diseases with germline pathogenic variants in the PTEN gene. Cowden syndrome is included in this syndrome . PTEN (phosphatase and tensin homolog) is a tumor suppressor gene located on chromosome 10q22-23; nearly 60%-90% of pathogenic variants are inherited. Cowden syndrome is a rare autosomic dominant condition, affecting approximately 1/200,000 people worldwide. Patients present benign and, malignant neoplasms in multiple organs, mostly breast and thyroid. The skin is the organ affected most consistently by Cowden disease. It is an autosomal dominant condition, characterized clinically by the presence of innumerable verrucous lesions on the skin. Interpretations of histopathologic findings in the cutaneous and mucosal lesions continue to be a matter of debate.

Lupus Erythematosus Tumidus: Clinical and Pathological Features in a Series of 20 Patients.

OBJECTIVE: We sought to assess the clinicopathologic/immunophenotypical features in patients with lupus erythematosus tumidus (LET). METHODS: All skin biopsies diagnosed as LET in 16 years were retrieved from our pathology laboratory. Clinical charts were reviewed and immunohistochemical markers were performed. Subpopulations of cells in the infiltrates were studied, as well as the number/distribution of plasmacytoid dendritic cells (PDC), which were compared with two control groups: normal skin and discoid lupus erythematosus. Direct immunofluorescence was performed when available. RESULTS: We found 20 patients (11 men and 9 women; mean age 43.5 years); the mean evolution previous to diagnosis was 20.3 months. They all had erythematous, nonscarring urticarial-like plaques: 8 in the head region only, 8 in trunk/limbs only; both segments were affected in 2 patients; topography was unknown in 2. Except for 1 patient, no one developed systemic lupus erythematosus. A dense perivascular/periadnexal superficial-to-deep lymphocytic infiltrate and stromal mucin deposition were characterized histopathologically; interphase changes were absent. Immunophenotype supported an inflammatory profile. The differential count of CD123 + PDC in 10/20 cases of LET (n = 1180) was notably higher than 5 cases of discoid lupus erythematosus (n = 419) and 5 cases of normal skin (n = 38). No immune deposits were found in 2 cases. CONCLUSION: LET is a rare, peculiar form of cutaneous lupus erythematosus that only exceptionally evolves to systemic lupus erythematosus . Its clinical-pathologic/immunophenotypical features are very characteristic. The amount of CD123 + PDC is a very helpful feature among the criteria for its diagnosis and seems to be relevant in its pathogenesis.

The use of azathioprine in atopic dermatitis: A review.

Most patients with atopic dermatitis (AD) have a good response to topical treatment. However, some need systemic therapy in order to satisfactorily control the disease. Azathioprine is an accessible drug for patients in many countries, including underdeveloped countries, and therefore it is used by many dermatologists in moderate and severe AD. It is important to have a deep knowledge and understanding about this drug since it is an alternative therapy as a steroid-sparing agent and an affordable one. However, when it comes to systemic therapy for AD, it is not always clear its indications and it is necessary to have a closer follow-up of the patient. In this paper, we describe thoroughly its indications in AD, the mechanism of action of the drug, as well as the interactions, adverse effects, adequate monitoring, and precautions in special population that must be considered when prescribing azathioprine. This review will help dermatologists prescribe it safely to all patients who require it.

Spironolactone in dermatology.

Spironolactone is a drug, similar in structure to aldosterone and acts as an aldosterone receptor antagonist with an anti-androgenic effect. This drug has proven to be useful in several dermatological entities, however its use has not been well explored. Its use in diseases such as acne has opened the door to the possibility of new therapies depending on the clinical manifestations of the patients, as well as its possible to use it as a first line treatment. Other diseases associated with the use of spironolactone where its effects have been shown to be useful are hidradenitis suppurativa, hirsutism, and female pattern androgenetic alopecia. In this review, we discuss the use of spironolactone in different skin diseases that are common in our environment, dosage according to different studies, treatment recommendations and adverse effects; all of the above mentioned in order to use this drug in a daily clinical practice.

Alibert and His Contribution to Dermatology (1768-1837).

ABSTRACT: Jean Louis Marc Alibert, 1786-1837, France, is considered one of the founders of modern dermatology, he was able to organize the Hôpital Saint Louis in Paris and developed a school, among other contributions he wrote at least two books, he described the tumoral stage of mycosis fungoides, congenital nevus, keloids, and proposed The Tree of Dermatoses as his concept for the understanding of skin diseases.

Clinicopathologic Features of Hydroa Vacciniforme-Like Lymphoma: A Series of 9 Patients.

Hydroa vacciniforme-like lymphoma is a recently recognized cutaneous T-cell lymphoma associated with Epstein-Barr virus. The disease is observed in children of Latin American or Asian ethnicity. The authors report the clinical, histopathological, and immunophenotypical features of 9 new Mexican patients (M:F = 2:1; mean age, 14.5 years; median age, 13.3 years; age range, 4-27 years), expanding on previous observations of this elusive disease. The most common clinical aspects were persistent facial edema with necroses and pitted scars. Histopathological analyses revealed variably dense lymphoid infiltrates with common angiodestructive features. Neoplastic cells expressed CD3 and cytotoxic markers in all cases and were constantly positive for Epstein-Barr virus (EBER-1). Expression of other markers was variable. Follow-up data revealed that all patients died within 6 months or less, thus showing a very aggressive course with poor prognosis.

Congenital melanocytic nevus: two clinicopathological forms.

Congenital melanocytic nevus (CMN) is a hamartomatous disease for which many attempts at classification have been proposed. This disease is relevant not only because of its functional and esthetic implications but also because it is a well-documented precursor to malignant melanoma. We performed a clinical and pathological prospective study of 200 cases of CMN and were able to identify 2 different forms of CMN, each one with biological, clinical, and histopathological features and criteria that are consistent and repeatable. We propose to name them types I and II. Type I CMN is the most common, usually, if not always, a single lesion, it consists of a plaque that involves only 1 anatomic region and does not go beyond it; type I CNM grows in proportion to the growth of the child, melanoma rarely develops from it, and when it does it usually arises at the dermoepidermal junction. Its histopathology shows cords, strands, nests, and single units of melanocytes spreading between collagen bundles only in the dermis and frequently the epidermis too, but without trespassing to the hypodermis, that is, it is superficial. Type II CMN is always made up of many lesions, one of them being very large and surrounded by many lesions; histopathologically, it involves not only the skin but also deeper structures, sometimes bone and central nervous system; therefore, it is deep; when melanoma develops, it does in the dermal component and usually from the largest plaque. This type of CMN is the one that develops neurocutaneous melanocytosis. This system is not only easy and logical but it also has biologic advantages and the clinical-pathological correlation and criteria are repeatable by clinicians and pathologists.

Cutaneous amebiasis: 50 years of experience.

Although cutaneous amebiasis (CA) is a rare disease, it is a public health concern worldwide, particularly in developing nations. It gains importance because of its severe clinical course, which can be confused with other disorders. Therefore, knowledge of its clinical features, histopathology, and pathogenesis is essential. We present a retrospective analysis over 50 years of 26 patients with CA who were diagnosed and treated at 2 Mexican institutions. Our main focus was to draw clinical information to identify mechanisms by which amebae reach the skin, occurring in a relatively small percentage of infected individuals. The recorded data included age and sex of the patients, form of presentation, any associated illnesses and/or factors, and methods for diagnosis. Histologic slides were reviewed in all cases; cytologic preparations also were available for 6 cases. Most patients were male (overall male to female ratio, 1.9 to 1). The disease always presented as painful ulcers containing varying amounts of amebae microscopically; the amebae were fairly easy to identify with routine stains, particularly when examination of tissue or smears was prepared from the edges of the ulcer instead of the necrotic centers. Erythrophagocytosis by the trophozoites was found and represented an unequivocal sign of its pathogenicity. We review the 2 mechanisms by which the organisms reach the skin. Most cases resolve with the use of specific antiamebic drugs; however, if left untreated, progression is rapid and unrelenting, sometimes with massive destruction of skin and subcutaneous tissues. Therefore, CA is a particularly virulent form of amebiasis.

Variable sampling approach to mitigate instability in networked control systems with delays.

This paper analyzes a new alternative approach to compensate for the effects of time delays on a dynamic networked control system (NCS). The approach is based on the use of time-delay-predicted values as the sampling times of the NCS. We use a one-step-ahead prediction algorithm based on an adaptive time delay neural network. The application of pole placement and linear quadratic regulator methods to compute the feedback gains taking into account the estimated time delays is investigated.

A variant of lymphomatoid papulosis simulating primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma. Description of 9 cases.

Lymphomatoid papulosis (LyP) is a recurrent, self-healing eruption belonging to the spectrum of cutaneous CD30+lymphoproliferative disorders. Three main histologic subtypes of LyP are recognized: type A (histiocytic), type B (mycosis fungoides-(MF)-like), and type C (anaplastic large cell lymphoma-like). We reviewed 26 biopsies from 9 patients (M:F=6:3, median age: 29; mean age 27,2; age range 10 to 38) who presented with clinical features typical of LyP but with histopathologic aspects that resembled primary cutaneous aggressive epidermotropic CD8+cytotoxic T-cell lymphoma. In all but 1 case atypical lymphoid cells showed expression of CD30, and in 8 of 9 cases a T-cell cytotoxic phenotype could be observed (betaF1+, CD3+, CD4-, CD8+). Expression of at least 1 cytotoxic marker (TIA-1, granzyme B) was observed in all cases. Polymerase chain reaction analysis of the T-cell receptor genes revealed a monoclonal rearrangement in 2 of 5 cases tested. Follow-up data available for 8 patients (mean follow-up time: 84 mo, median: 32.5 mo; range: 1 to 303 mo) revealed that none of them developed systemic involvement or signs of other cutaneous lymphomas. This cytotoxic variant of LyP may be histopathologically indistinguishable from primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma, and may be the source of pitfalls in the diagnosis and classification. We propose the term LyP type D for this unusual variant of the disease. Accurate clinicopathologic correlation is required in this setting, with crucial implications regarding prognosis and management of patients.

Skin metastasis from hepatocarcinoma.

Cutaneous metastases may be the first sign of an internal neoplasm; hepatocellular carcinoma is a very rare source of skin involvement and presents with a protean morphology: papules, nodules, and masses that may be by natural sources or by artificial mechanisms. We present a 41-year-old man with hepatocellular carcinoma and hepatic cirrhosis who developed metastatic disease, which in the skin showed as a pyogenic granuloma. We analyze 38 cases from the literature and present a practical review of the subject.

Lucio's phenomenon is a necrotizing panvasculitis: mostly a medium-sized granulomatous arteritis.

Lucio's phenomenon (LPh) is a vasculitis clinically described in 1852 and microscopically documented in 1948 in patients with diffuse lepromatous leprosy; however, at present, there is no a clear concept about the pathogenesis of the necrosis, or about the type, size, and site of the damaged vessel. The objective of this study was to elucidate the type, size, site, and form of vessel damage in LPh in a retrospective, clinical, and histopathological study. Clinical information was obtained from the charts and records and/or from the histopathology request. Slides stained with hematoxylin and eosin, Ziehl-Neelsen, and Fite-Faraco were retrieved from our files. Direct immunofluorescence had been performed in 6 cases. Twelve cases fulfilled clinical evidence to make unequivocal diagnosis of diffuse lepromatous leprosy with LPh. All of them had necrotic, irregular, purpuric, and/or ulcerative lesions, which under the microscope showed medium-sized arteries, with their walls involved by clusters of macrophages containing large amounts of bacilli, distortion of the structure of the vessel wall, narrowing, and obliteration of their lumen. Smaller vessels showed changes of the leukocytoclastic type. LPh is a distinctive type of granulomatous and necrotizing panvasculitis; the involved vessels are mostly medium-sized arteries, located deeply in the skin, at the base, and within the hypodermis, but any other vessel is likewise involved, their occlusion leads to ischemic necrosis of the whole skin, frequently with detachment of the epidermis. These changes explain clearly and logically the clinical features observed more than 150 years ago.

Cutaneous amebiasis in pediatrics.

BACKGROUND: Cutaneous amebiasis (CA), which is still a health problem in developing countries, is important to diagnose based on its clinical and histopathologic features. OBSERVATIONS: Retrospective medical record review of 26 patients with CA (22 adults and 4 children) treated from 1955 to 2005 was performed. In addition to the age and sex of the patients, the case presentation, associated illness or factors, and method of establishing the diagnosis, clinical pictures and microscopic slides were also analyzed. CONCLUSIONS: Cutaneous amebiasis always presents with painful ulcers. The ulcers are laden with amebae, which are relatively easy to see microscopically with routine stains. Erythrophagocytosis is an unequivocal sign of CA. Amebae reach the skin via 2 mechanisms: direct and indirect. Amebae are able to reach the skin if there is a laceration (port of entry) and if conditions in the patient are favorable. Amebae are able to destroy tissues by means of their physical activity, phagocytosis, enzymes, secretagogues, and other molecules.