By B. Reto. University of San Francisco. 2018.

In persons with earlier age of onset purchase 20 mg erectafil amex, psoriasis is more likely to be severe Key Concept/Objective: To understand the epidemiology of psoriasis The estimated prevalence of psoriasis ranges from 0 erectafil 20 mg lowest price. The reasons for the geographic variation in prevalence are unknown, but climatic factors and genetics may play a role. On the basis of a survey mailed to 50,000 households, the prevalence in the United States is estimated to be 2. Psoriasis can occur in patients of any age, with some cases being reported at birth and others being reported in patients older than 100 years. The average age of onset is 23 years in the United States. Psoriasis occurs with equal frequency in men and women. In populations in which there is a high prevalence of pso- riasis, onset tends to occur at an earlier age. In persons with earlier age of onset, psoriasis is more likely to be severe, with involvement of a large area of skin surface. It has long been known that psoriasis improves when patients are exposed to sunny climates and to regions of lower latitude. In northern latitudes, exacerbation of psoriasis commonly occurs during 6 BOARD REVIEW the fall and winter. An 18-year-old college student presents to the student health clinic for evaluation of a rash. The patient was recently evaluated for sore throat and diagnosed with streptococcal pharyngitis. Physical examina- tion reveals small, scaling erythematous papules on the trunk and bilateral extremities. This patient’s clinical presentation is most consistent with which clinical variant of psoriasis? Pustular Key Concept/Objective: To be able to differentiate among the clinical variants of psoriasis Nearly 90% of psoriasis patients have plaque-type psoriasis, a form that is characterized by sharply demarcated, erythematous scaling plaques. The elbows, knees, and scalp are the most commonly affected sites. The intergluteal cleft, palms, soles, and genitals are also commonly affected, but psoriasis can involve any part of the body. Lesions frequently occur in a symmetrical pattern of distribution. Many patients have only one or a few lesions that persist for years and that occasionally resolve after exposure to sunlight. Other patients can be covered with plaques that become confluent, affecting nearly 100% of the body surface area. Nail involvement is common, particularly in patients with severe dis- ease. The second most common form of psoriasis, guttate psoriasis, affects fewer than 10% of patients and is characterized by the development of small, scaling erythematous papules on the trunk and extremities. This form of psoriasis often occurs after streptococ- cal infection. Patients with plaque-type psoriasis can develop guttate psoriasis. Conversely, patients with guttate psoriasis frequently develop plaque-type psoriasis. Erythrodermic psoriasis is a severe form of psoriasis that often affects the entire cuta- neous surface. Patients present with an exfoliative erythroderma in which the skin is very red and inflamed and is constantly scaling. Patients are acutely ill, their skin having lost all protective function. Loss of temperature control, loss of fluids and nutrients through the impaired skin, and susceptibility to infection make this a life-threatening condition. Some patients present with erythrodermic psoriasis de novo; others develop erythrodermic psoriasis after having typical plaque-type or guttate psoriasis. Erythrodermic psoriasis can occur after withdrawal of systemic corticosteroids, after phototherapy burns, as a result of antimalarial treatment, as a result of a drug-induced hypersensitivity reaction, or for no apparent reason. Erythrodermic psoriasis has been associated with cutaneous T cell lym- phoma. Pustular psoriasis, another severe form of the disease, can occur in patients with pre- existing psoriasis, or it can arise de novo. Pustular psoriasis can be generalized (von Zumbusch-type) or localized to the palms and soles. In either case, the condition is severe and debilitating. In generalized pustular psoriasis, the body is covered with sterile pustules. As with erythrodermic psoriasis, the protective functions of the skin are lost, and patients may succumb to infection or hypovolemia and electrolyte imbalance caused by loss of fluid through the skin.

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This conversion may take cinomas that produce excess androgens (e generic erectafil 20 mg online. Sudden onset of acne or treatment-resistant acne been identified by several investigators [16–18] buy erectafil 20mg line. There are may be associated with hyperandrogenism from causes two known forms or isozymes of 3ß-HSD. The type I iso- such as an adrenal or ovarian tumor or from conditions zyme is active in skin, placenta and mammary tissue, such as congenital adrenal hyperplasia or polycystic ovary whereas the type II isozyme is active in the adrenal gland disease. Conversely, it has been observed that men with and the gonads. The major isozymes of steroid- androgen insensitivity (nonfunctional androgen recep- metabolizing enzymes that are active in human sebaceous tors) do not produce adult levels of sebum and they do not glands are listed in table 1. This clinical observation implies that a 58 Dermatology 2003;206:57–67 Thiboutot/Chen Fig. Biochemical pathway of sex steroid hormone metabolism. HSD = Hydroxyste- roid dehydrogenase; 5·-R = 5·-reductase. Another important enzyme that is found within the Table 1. Predominant isozymes of steroid metabolizing enzymes skin is 17ß-hydroxysteroid dehydrogenase (17ß-HSD). It is responsible for con- 17ß-Hydroxysteroid dehydrogenase type 2 verting the weak androgen androstenedione into the more 5·-Reductase type 1 potent androgen testosterone. It can also interconvert weak and potent estrogens such as estrone and estradiol. Testosterone in turn can be produced from androstene- dione. To date, seven types of human 17ß-HSDs have been cloned, sequenced, and characterized, designated active within the sebaceous gland and in keratinocytes types 1–7 in the chronological order of their isolation [20– derived from the infrainfundibular region of piloseba- 23]. Recently, the type 8 17ß-HSD also known as Ke6 ceous follicle (from the base of the epidermis to the point gene was shown to efficiently transform estradiol to estro- of insertion of the sebaceous duct) [3, 29]. The type 2 iso- gen in transfected HEK-293 cells. The type 2 isozyme zyme is most active in the prostate gland where it can be of 17ß-HSD appears to be the most active within the seba- inhibited by drugs such as finasteride. While the type 1 ceous gland where it prefers to oxidize testosterone back 5·-reductase has a broad alkaline pH optima of 6. In this regard, the 17ß-HSD and demonstrates relatively moderate affinity for steroid enzyme may play a protective role in the skin by metabo- substrates (Km = 1–5 ÌM), the type 2 5·-reductase has a lizing testosterone back to the less potent precursor, narrow acidic pH optimum of 5. It may also represent a regulatory point high affinity for substrates (Km = 4–50 nM) [30, 31] in androgen and estrogen metabolism within the skin. Activity of 5·-reductase and 17ß-HSD exhibits region- Dihydrotestosterone is produced from testosterone al differences depending upon the source of the sebaceous within peripheral tissues such as the skin by the action of glands [25, 29] (fig. In skin that is prone to acne, such the 5·-reductase enzyme. Recently, two isozymes of 5·- as facial skin, activity of the type 1 5·-reductase in seba- reductase have been identified. The type 1 isozyme is ceous glands is greater than in sebaceous glands obtained Update and Future of Hormonal Therapy Dermatology 2003;206:57–67 59 in Acne from nonacne-prone skin. Enzymes involved in lipogenesis in human sebaceous being produced in sebaceous glands from facial skin com- glands pared to other areas of the body that are not prone to Enzymes involved in Enzymes involved in develop acne. In contrast, the oxidative activity of the cholesterol synthesis fatty acid synthesis type 2 17ß-HSD enzyme is greater in sebaceous glands from nonacne-prone areas compared to sebaceous glands Acetoacetyl CoA thiolase Acetyl CoA carboxylase obtained from facial skin. Since the predominant activity HMG CoA synthetase Fatty acid synthetase HMG CoA reductase of this isozyme is to transform testosterone back to its less Mevalonic acid kinase active precursor, it may be inferred that facial skin is less Mevalonate decarboxylase able to metabolize testosterone to its less potent precur- Isopentenyl pyrophosphate isomerase sor. The net effect of the activity of these two enzymes is Geranyl transferase the greater production of potent androgens such as T and Squalene synthetase Squalene oxidocyclase DHT within sebaceous glands of facial areas that may in part account for the development of acne in these areas. Site of Androgen Action in Acne The sebaceous gland is known to be a site of androgen regulating the production of growth factors by dermal action within the pilosebaceous unit. The stromal/epithelial interaction of sex ste- hypothesized that androgens may play a role in follicular roid hormones and growth factors is an important phe- hyperkeratinization in acne in addition to their effects on nomenon in the local regulation of other endocrine- stimulating sebum secretion [1, 2]. Indirect evidence in responsive tissues such as the prostate, breast, endometri- support of this hypothesis includes the finding of andro- um and ovary. Evidence exists for the importance of these gen receptors in the outer root sheath of sebaceous folli- autocrine and paracrine effects of androgens and growth cles, the clinical observation that antiandrogens may factors in the regulation of sebaceous glands. In addition reduce follicular casts and the finding of activity of andro- to androgen receptors, sebocytes also possess receptors for gen-metabolizing enzymes such as 3ß-HSD, 17ß-HSD growth factors such as epidermal growth factor (EGF) and and 5·-reductase in follicles. Furthermore, the activity of insulin-like growth factor I (IGF-I).

Porous hydroxyapatite and tricalcium phosphate cylinders with two different pore size ranges implanted in the cancellous bone of rabbits cheap erectafil 20 mg otc. Tampieri A generic erectafil 20mg visa, Celotti G, Spiro S, Delcogliano A, Franzese S. Porosity-graded hydroxyapatite ceramics to replace natural bone. Immediate bone forming capability of prefabricated osteogenic hydroxyapatite. Okamura A, Goto M, Goto T, Yoshinari M, Matsuko S, Katsuki T, Tanaka T. Substrate effects to initial attachment and subsequent behaviour of human osteoblastic cells (Saon-2). Daculsi G, Passuti N, Martin S, Deudon C, Legeros RZ, Raher S. Macroporous calcium phosphate ceramic for long bone surgery in humans and dogs. Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function. Deligianni DD, Katsala ND, Koutsoukos PG, Missirlis YF. Effect of surface roughness of hydroxyap- atite on human bone marrow cells adhesion, proliferation, differentiation and detachment strength. Osteogenesis in extraskeletally implanted porous calcium phosphate ceramics: variability among different kinds of animals. A histomorphometric study of the tissue reaction around hydroxyapatite implants irradiated after placement. Repair of bone defects with marrow cells and porous ceramics. Bonding osteogenesis in coraline hydroxyapatite combined with bone marrow cells. Frayssinet P, Primout I, Rouquet N, Autefage A, Guilhem A, Bonnevialle P. Osteogenic potential of allogenic rat marrow cells in porous hydroxyapatite ceramics. Bareille R, Lafage-Proust MH, Faucheux C, Laroche N, Wenz R, Dard M, Amedee J. Various evaluation techniques of newly formed bone in porous hydroxyapatite loaded with human bone marrow cells implanted in an extra-osseous site. Petite H, Viateau V, Bensaid W, Meunier A, de Pollak C, Bourguignon M, Oudina K, Sedel L, Guillemin G. The origin of bone formed in composite grafts of porous calcium phosphate ceramic loaded with marrow cells. Interaction of osteogenic cells with hydroxyapatite implant materials in vitro and in vivo. Sun JS, Tsuang YH, Liao CJ, Liu HC, Hang YS, Lin FH. The effects of calcium phosphate particles on the growth of osteoblasts. Glass reinforced hydroxyapatite for hard tissue surgery. Biocompatibility tests on a novel glass–ceramic system. Oonishi H, Hench LL, Wilson J, Sugihara F, Tsuji E, Kushitani S, Iwaki H. Comparative bone ingrowth behaviour in granules of bioceramic materials of various sizes. Sautier JM, Kokubo T, Ohtsuki T, Nefussi JR, Boulekbache H, Oboeuf M, Loty S, Loty C, Forest N. Bioactive glass–ceramic containing crystalline apatite and wollastonite initiates biomineralization in bone cell cultures. Interaction of bioactive glasses with peritoneal macrophages and monocytes in vitro. Gao TJ, Lindholm TS, Kommonen B, Ragni P, Paronzini A, Lindholm TC. Microscopic evaluation of bone–implant contact between hydroxyapatite, bioactive glass and tricalcium phosphate implanted in sheep diaphyseal defects. Glant TT, Jacobs JJ, Molnar G, Shanbhag AS, Valyon M, Galante JO. Bone resorption activity of particulate-stimulated macrophages.