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Dermatological Abnormalities Hirsutism Acne and Androgenic Alopecia

Acne has been reported to affect 12-14 of white PCOS patients (10,60), although the prevalence of this dermatological abnormality also varies with ethnicity. It is reportedly higher in Asian Indians (60) and lower in Pacific Islanders (58). Androgenic alopecia is a recognized sign of PCOS (61-63) however, in a study of 257 androgen excess patients undergoing treatment, only 12 (4.7 ) complained of hair loss only (10). Overall, acne and androgenic alopecia apparently have a low prevalence among patients with PCOS. Because studies quantifying and determining the prevalence of acne and androgenic alopecia in a significant number of unselected patients with PCOS are lacking, we did not include these disorders in our calculations of economic burden.

Localised alopecia

Alopecia areata is a common form of hair loss. It is seen in 2 of patients attending the average dermatology clinic in the United Kingdom. There may be small patches of hair loss or the whole scalp may be affected. Resolution occurs in a few months or the condition may persist for years. There may be slight inflammation of the skin in the affected areas in keeping with the possibility of an underlying immune reaction against the hair follicles. There is also an association with autoimmue disease and atopy. In the affected areas the follicles are visible and empty. The hairs about to be lost have an exclamation mark appearance and in some areas that are resolving, fine vellus hairs are seen. Patches commonly occur on the scalp, face, or eyebrows. In alopecia totalis, the whole head is involved, and in alopecia universalis hair is lost from the whole of the body. In many patients, particularly if it is a first episode, regrowth occurs within a few months with fine pale hairs appearing...

Hair loss

Lupus Hair Loss Pattern

This is known as alopecia, said to be derived from the Latin alopex , a fox, presumably because of the bald patches of mange seen in wild foxes. Adult male pattern alopecia is so common as to be considered normal. Circulating levels of testosterone are not Adult pattern of alopecia comparison between men and women raised in bald men but there is evidence that availability of the hormone to the hair follicle is increased. In postmenopausal women there may be widespread thinning of the hair but loss of hair at the temples often occurs to some degree at an earlier age. Alopecia may be diffuse or localised. If it is simply due to a physiological derangement of hair growth, the follicles remain intact, whereas inflammation may lead to scarring and loss of the hair follicles. Hence, hair loss can be classified into the categories shown in the illustration on the right. Adult pattern of alopecia comparison between men and women - Alopecia Classification of alopecia Classification of alopecia

Diffuse hair loss

Alopecia Areata Diffuse

An interruption of the normal hair cycle leads to generalised hair loss. This may be due to changes in circulating hormones, drugs, inflammatory skin disease, and stress of various types. Telogen effluvium occurs if all the hairs enter into the resting phase together, most commonly after childbirth or severe illness. Two or three months later the new anagen hair displaces the resting telogen hair, resulting in a disconcerting, but temporary, hair loss from the scalp. Stress of any type, such as an acute illness or an operation, causes a similar type of hair loss. Postfebrile alopecia occurs when a fever exceeds 39 C, particularly with recurrent episodes. It has been reported in a wide range of infectious diseases, including glandular fever, influenza, malaria, and brucellosis. It also occurs in fever associated with inflammatory bowel disease. Dietary factors such as iron deficiency and hypoproteinaemia may play a role, but are rarely the sole cause of diffuse alopecia. Congenital...

Preface to the Second Edition

Thanks to the positive reception of the first edition of the book by the medical community both in Europe and in the USA, the present book has come to its second edition. All the chapters have been thoroughly revised and two new chapters on Vitiligo and Alopecia areata were included.

The Composition of Cells

Despite their differences, most cells have a great deal in common with each other. Every cell, whether a Archaea at the bottom of the ocean or a cell in a hair follicle on the top of your head has certain basic qualities they contain cytoplasm and genetic material, are enclosed in a membrane and have the basic mechanisms for translating genetic messages into the main type of biological molecule, the protein. All eucaryotic cells share additional components. Each of these basic parts of a cell is described briefly below

Assessment of the patient

As well as assessing the clinical changes, the effect of a skin condition on the patient's life and their attitude to it must always be taken into account. For example, severe pustular psoriasis of the hands can be devastating for a self employed electrician and total hair loss from the scalp very distressing for a 16 year old girl.

Table 34 Causes and associations of trachyonychia

Lichen Planus Finger Nails

Idiopathic (twenty-nail dystrophy) (Figure 3.34) Alopecia areata (Figure 3.32) Lichen planus (Figures 3.37, 3.38) Eczematous histology Chemicals and alopecia areata makes it common to observe trachyonychia in other conditions frequently associated with alopecia areata, such as atopic dermatitis, ichthyosis or Down's syndrome. Table 3.4 lists the known causes and associations of trachyonychia.

Adaptation to Cancer

Surgery often requires a great amount of recuperation, sometimes causes new physical problems, and may cause substantial disfigurement. Radiation and chemotherapy often cause significant side effects, including hair loss, sterility, even nausea and vomiting, fatigue, and diarrhea. Anticipatory anxiety, classically conditioned by these treatments, may increase the severity of many of these symptoms. In the long term, cancer patients face problems with physical, psychological, and sexual functioning, as well as family and work difficulties. Many studies have demonstrated that cancer patients exhibit increased rates of depression, and some have demonstrated increased rates of anxiety. Behaviorists working in treatment settings have attempted to help individuals with cancer cope as well as possible with these difficulties.

Other organspecific autoimmune diseases of the skin

Alopecia areata There is evidence that this condition may be associated with an immune reaction against the hair follicle. The increased incidence of antibodies to the thyroid gland and gastric parietal cells in patients with alopecia areata provides circumstantial support for an autoimmune aetiology.

Acute Localized Otitis Externa

This disorder, a different disease from the diffuse type, also presents with a very painful ear. It is otherwise known as a furuncle of the canal. The infection is localized in an obstructed sebaceous gland or hair follicle out near the meatus. A tender red, raised pustule is readily seen occluding the meatus (Fig. 4.6). Staphylococcus aureus is the usual offender here, and appropriate oral antibiotics such as cephalosporins or amoxicillin clavulanate, as well as topical neomycin preparations, are indicated. When bulging and soft, incision and drainage at the most fluctuant point with a 11 blade will benefit.

Summary of Predictive Value of Clinical Markers

Overall, between 50 and 75 of women with evidence of hirsutism or the complaint of unwanted hair growth will have androgen excess, notably PCOS. Alternatively, only 20 and 40 of patients with acne as their sole presenting complaint and only about 10 of women complaining of hair loss will have androgen excess. Between one-fourth and one-third of women with oligo- amenorrhea have androgen excess, and only about one-fifth of women with polycystic ovaries on ultrasonogra-phy will have androgen excess.

Nonorganspecific skin autoimmune disease

The hallmark of this condition is the presence of antibodies against various components of the cell nucleus. Although a wide range of organs may be affected, in three quarters of the patients the skin is involved, generally with an erythematous eruption occurring bilaterally on the face in a butterfly distribution. There may also be photosensitivity, hair loss, and areas of vasculitis in the skin. There is often intolerance of

Mammalian orthoreovirus 1Lang MRV

Experimental infection of mice causes jaundice, alopecia, conjunctivitis and 'oily hair' associated with steatorrhea. The mice appear to have been dipped in oil, and if newborn mice are infected their growth is stunted and they become runts. There is no clear association with disease in humans and infections are usually symptomless.

Benefits Versus Toxicity And Risks Of Therapy

Chemotherapy can be divided into those of the CMF-like regimens and those of the doxoru-bicin regimens. All chemotherapies used as adjuvant treatment cause significant myelosup-pression, with leukopenia generally clinically more significant than anemia or thrombocy-topenia. In the NSABP trials of classic CMF x 6, the incidence of neutropenia less than 2,000 was 10 percent and severe infection about 1 percent.21 With AC x 4, it is 4 percent severe neutropenia and 2 percent severe infec-tion.21 With 6 months of CAF, the risk of leukopenia and infection is higher. Thrombocy-topenia is seen in less than 1 percent of patients in most regimens.21 Doxorubicin-containing regimens are more emetogenic than CMF however, the incidence of severe vomiting is rapidly dropping with the introduction of serotonin antagonists. Alopecia is nearly universal with doxorubicin and is seen in about 40 percent of CMF patients.21 Diarrhea is rarely seen with either regimens the use of serotonin antagonist...

Thymus and Reproduction

The thymus plays an important role in the immune system, and it has been suggested that thymic cells and peptides play a role in determining reproductive lifespan in females (Bukovsky and Presl 1979 Rebar 1982 Suh et al. 1985). The relationship of age-associated thymic involution with diminution of ovarian function is supported by the alteration of ovarian function in neonatally thymectomized mice (Nishizuka and Sakakura 1969). In addition, in congenitally athymic (nude) mice, follicular loss is first evident at two months of age and this is specifically due to a reduction in the numbers of primary follicles. The first ovulation is delayed until two and half months of age, compared to the first ovulation in the one and half month old normal mouse females. By four months, an overall reduction in all fractions of the follicle population occurs in nude mice, and ovulation ceases (Lintern Moore and Pantelouris 1975). Interestingly, the absence of the thymus might also be responsible for...

Polymorphisms in the 5 Alpha Reductase Gene

The 5 a-reduction of testosterone to the potent androgen dihydrotestosterone (DHT) is catalyzed by the 5 a-reduc-tase enzymes. Two forms of the 5 a-reductase enzyme have been described current nomenclature designates these as type I and type II enzymes. A TA repeat is present in the 31 untranslated region of the type II gene. After examination of appropriate data sets, Kantoff et al.17 concluded that there was no relationship between type II 5 a-reductase TA repeat length and prostate cancer risk.

Signaling Milieus At The Effector Sites

Systemic hormones support mucosal immune functions at several different effector sites. Ventral prostate and urethral gland epithelial cells express pIgR, and IgA+ cells populate the underlying tissue spaces, and castration decreases pIgR expression. In the rat, the effect of castration can be reversed by either estradiol or dihydrotestosterone, but neither hormone has a substantial effect on IgA+ cell content (91). In contrast, testosterone prevents the effects of castration on both pIgR expression and IgA+ cell number in the mouse prostate and urethral glands (92). To the extent data on the mouse prostate and urethral glands are available, they resemble the extensive body of data on hormonal influences on pIgR expression and IgA+ cell infiltration in the rodent lacrimal gland that has been published by Sullivan et al. (93,94).

Thick Eyebrows Syndrome

Low Set Breast Microcephaly Syndrome

In the ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome there are varying manifestations of lobster-claw deformity (ectrodactyly) of the hands and feet and there is cleft lip palate. The cleft lip is usually bilateral. Other manifestations include absence of the lacrimal puncta with tearing and blepharitis abnormal teeth malformations of the genitourinary (GU) tract such as cryptorchidism and alterations in the skin and hair. Scalp hair, eyelashes and eyebrows are usually sparse and hair color is light. The nails may be hypoplastic and brittle. Most of these infants have normal intelligence. In this infant note the severe bilateral cleft lip and palate. Figure 3.20. In the ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome there are varying manifestations of lobster-claw deformity (ectrodactyly) of the hands and feet and there is cleft lip palate. The cleft lip is usually bilateral. Other manifestations include absence of the lacrimal puncta with tearing...

Table 43 Causes and associations of onychogryphosis Dermatological

Pityriasis Rubra Pilaris Nails

Positive, homogeneous, rounded or oval, amorphous masses surrounded by normal squamous cells which are usually separated from each other by empty spaces caused by the fixation process. These clumps, which coalesce and enlarge, have been described in psoriasis of the nail, onychomycosis, eczema and alopecia areata, and also in some hyperkeratotic processes such as subungual warts and pincer nails. The horny excrescences of the nail bed are not very obvious, but the ridged structure may become apparent if the nail plate is cut and shortened.

Options for Hormonal Therapy

Within the class of androgen receptor blockers, the drug options are spironolactone, cyproterone acetate, and flutamide. In the United States, spironolactone is the drug most commonly used. Oral spironolactone decreases sebum excretion rate and inhibits the type 2 17P-HSD 48, 49 . Recommended doses for the treatment of acne are 50-100 mg, taken with meals 50 . However, many women respond well to 25 mg twice daily, and some even respond to just 25 mg a day. These low doses in healthy young women are well tolerated. However, if this drug is used in older women with other possible medical problems, or if higher doses are used for conditions such as hirsutism or androgenic alopecia, serum electrolytes should be monitored. Side effects to be aware of include breast tenderness and menstrual irregularities. Flutamide, a very potent antiandrogen that is also used to treat prostate cancer, can be used in the treatment of acne, hirsutism, and androgenic alopecia 52 . It can be given in doses of...

New Developments and Future Trends

Leukotrienes Inflammatory Mediators

The inhibitors of 5a-reductase isoenzymes (1 and 2) can be schematically divided in three groups according they substrate specificity Pure or preferential inhibitors of 5a-reductase 1, pure or preferential inhibitors of 5 a-reductase 2, and dual inhibitors 26, 120 . Despite the fact that several steroidal and non-steroidal inhibitors have been synthesized and experimented in pharmacological models, only finasteride has been extensively used for clinical purposes, namely benign prostate hyperplasia and male baldness with positive results. In women, finasteride has been used in some control trials for treatment of hirsutism with an objective favorable response. On the basis of experimental observations on distribution of 1 and 2 isoenzymes in human skin, scalp and prostate, the pure 5 a-

Physiology The Unity ofCompanies 2003 Form and Function Third Edition

Decay, such as formalin. flagellum (fla-JEL-um) A long, motile, usually single hairlike extension of a cell the tail of a sperm cell is the only functional flagellum in humans. fig. 27.18 flexion A joint movement that, in most cases, decreases the angle between two bones. Compare extension. fig. 9.9 fluid balance See water balance. fluid compartments Any of the major categories of fluid in the body, separated by selectively permeable membranes and differing from each other in chemical composition. Primary examples are the intracellular fluid, tissue fluid, blood, and lymph. fluid-mosaic model The current theory of the structure of a plasma membrane, depicting it as a bilayer of phospholipids and cholesterol with embedded proteins, many of which are able to move about in the lipid film. fig. 3.6 follicle (FOLL-ih-cul) 1. A small space, such as a hair follicle, thyroid follicle, or ovarian follicle. 2. An aggregation of lymphocytes in a lymphatic organ or mucous membrane....

Hormonal regulation and control of spermatogenesis

A stallion demonstrating Flehman. This typical behavioural response to sexual stimulation is driven largely by testosterone but also partly by dihydrotestosterone and GnRH. Fig. 3.26. A stallion demonstrating Flehman. This typical behavioural response to sexual stimulation is driven largely by testosterone but also partly by dihydrotestosterone and GnRH. The functions of the hypothalamus and the pituitary are also affected by testicular hormones. Testosterone has a negative feedback effect on both, reducing the concentration of GnRH released and the sensitivity of the anterior pituitary to GnRH stimulation (Thompson et al., 1979b Irvine et al., 1986). In response to this long negative feedback loop, the pituitary produces less LH. This negative feedback may also be attributed to the effect of dihydrotestosterone and possibly oestrogens and maybe progesterone (Amann, 1993b). As a result of this decline in LH levels, the stimulation of the Leidig cells is depressed, so...

Medical History and Physical Examination in Patients With Possible Androgen Excess

Modified Ferriman Gallwey Score

The timing and pace of pubertal development and its relation to complaints of unwanted hair growth, hair loss, acne, and or obesity should be established. The onset and progression of these complaints should also be established. Drug or medication use and exposure or use of skin irritants should be elicited. A detailed menstrual history should be obtained, with an emphasis on determining whether evidence of ovulatory function (e.g., premenstrual molimina) is present. Change in skin pigmentation or texture, extremity or head size, and changes in facial contour should be noted. A detailed family history of endocrine, reproductive, or metabolic disorders should be obtained. A family history of similar hyperandrogenic signs and symptoms is a powerful clue to the inherited basis of the disorder, although a familial association can be noted for PCOS, HAIR-AN syndrome, NCAH, and IH patients. Clinicians should note that the etiology of hirsutism can often be suspected from the history alone....

Ispinesib and related compounds

Ispinesib (SB-715992 CK0238273, 2), one member of a KSP inhibitor series bearing a quinazolinone core, was the first mitotic kinesin inhibitor to enter clinical trials. Like its earlier reported analog 1, ispinesib was reported to be an allosteric inhibitor of KSP that binds at the motor domain and inhibits its ATPase activity in an ATP uncompetitive manner. It was also shown to be 70,000-fold selective for KSP versus other members of the kinesin family. Results have been reported from two Phase I clinical trials with different dosing schedules. In trial KSP10001 11 , ispinesib was dosed i.v. once every 21 days (q21) in 45 patients. The drug was well tolerated without alopecia or prevalent neurotoxicity. At a dose of 21 mg m2, dose-limiting toxicities (DLT) were prolonged ( 5 days) neutropenia and febrile A second KSP inhibitor, SB-743921, entered clinical trials in 2004. Like ispinesib, it has been shown to be a very selective KSP inhibitor that is 40,000-fold more selective over...

Anovulation Is A Characteristic Feature Of Pcos. It Manifests As Menstrual Disturbance 80 Amenorrhoea Oligoamenorrhea

Patient With Hyperandrogenism

Patients with PCOS may present complaining of irregular or unpredictable menstrual cycles, unwanted hair growth, acne or scalp hair loss, or unexplained weight gain or overweight (see Section 2.1.4.). Another frequent presenting complaint of PCOS may be infertility, possibly associated with recurrent first trimester miscarriages. Approximately 30-50 of PCOS patients will complain of infertility at the time they are seen for their first visit (1,2). The development of hyperandrogenism in PCOS is usually associated with a slowly progressive clinical history and stable symptomatology by the mid to late 30s. As patients enter the fourth decade of life, their symptoms may improve, possibly associated with a decline in circulating androgen levels (6). Alternatively, the rapid development of symptoms, including hirsutism, oligo-amenorrhea, severe acne and alopecia, increased muscularity, and clitoromegaly, is indicative of a virilizing syndrome, most commonly caused by an androgen-producing...

Hosttargeted acaricides

Another recent approach, using bait boxes for the topical treatment of rodents with fipronil, is being evaluated for the control of I. scapularis on wild white-footed mice (patents pending, Aventis Environmental Science and Centers for Disease Control and Prevention). Discovered in 1987, fipronil is the first of a new class of insecticides, the phenyl pyrazoles, labelled for a broad range of insect pests on more than 50 crops and various non-crop uses (Aventis, 2000). Fipronil is a reversible inhibitor of the gamma-aminobutyric acid (GABA)-regulated chloride channel that displays selectively tighter binding in insects than in mammals. Percutaneous passage of the compound is low, with the compound concentrating in the epidermis, hair follicle and sebaceous glands (Cochet et al., 1997). Fipronil is commercially available for the control of fleas and ticks on

Infant Umbilical Hernia

Anophthalmia

In this infant with trigono-cephaly, hypotelorism, patchy alopecia, and eleven ribs, the diagnosis was that of a ring D chromosome defect (karyotype was performed in the pre-banding era). Trigonocephaly is associated with premature fusion of the metopic suture and may occur in chromosomal anomalies and in median cleft syndrome, but also occurs in normal infants. Figure 4.20. In this infant with trigono-cephaly, hypotelorism, patchy alopecia, and eleven ribs, the diagnosis was that of a ring D chromosome defect (karyotype was performed in the pre-banding era). Trigonocephaly is associated with premature fusion of the metopic suture and may occur in chromosomal anomalies and in median cleft syndrome, but also occurs in normal infants. Figure 4.21. This view better demonstrates the trigonocephaly and the patchy alopecia.

Hypothalamic and pituitary hormones

A feedback mechanism is known to exist that controls LH and FSH production in the stallion and which originates from the testes. In the absence of testes (for example, in geldings), LH levels are naturally high however, the administration of dihydrotestosterone to such animals results in a depression in LH secretion and eventually in LH production (Thompson et al., 1979b). This can be further demonstrated by the treatment of stallions with exogenous testosterone. Such treatment results in a reduction in circulating FSH levels (Ashley et al., 1986). Two other hormones, activin and inhibin, which originate in the testes are also known to be involved they have, respectively, an activating and inhibitory role on FSH production (Amann, 1993b).

Umbilical Venous Catheter

Umbilical Catheter Extravasation

Hypopigmentation, alopecia and scarring on the scalp of a former very low birth weight premature infant (birth weight 700 g) following multiple scalp vein infiltrations. Figure 7.25. Hypopigmentation, alopecia and scarring on the scalp of a former very low birth weight premature infant (birth weight 700 g) following multiple scalp vein infiltrations.

Other Dermatologic Problems

Infants With Abnormal Big Head

The typical facies of hypohidrotic (anhidrotic) ectodermal dysplasia is seen in this infant. Note the alopecia, absent eyebrows and eyelashes, square forehead with frontal bossing, hyperpigmented wrinkles around the eyes, flattened nasal bridge, and large conspicuous nostrils. There are wide cheek bones with depressed cheeks, thick everted lips, a prominent chin, and the ears may be small and pointed. These infants have a thin dry skin, decreased sweating, decreased tearing, and abnormal dentition. The nails are defective in a large percentage of these patients in that they may be thin, brittle, or ridged. If the absence of the sweat glands is generalized, they may have recurrent fever in high environmental temperatures.

Treacher Collins Syndrome

Treacher Collins Syndrome

The same infant when crying better demonstrates the findings. Note the antimongoloid slant, the prominent nose, and the micrognathia. Infants with this syndrome may have a cleft of the palate, particularly of the soft palate. A finding in many of these infants is a projection of the scalp hair onto the lateral cheek. Figure 3.194. The same infant when crying better demonstrates the findings. Note the antimongoloid slant, the prominent nose, and the micrognathia. Infants with this syndrome may have a cleft of the palate, particularly of the soft palate. A finding in many of these infants is a projection of the scalp hair onto the lateral cheek.

Androgens and Sebum Production

Acne Vulgaris

The majority of potent androgens are produced by peripheral target tissues. For example, in postmenopausal women, 100 of active sex steroids are synthesized in peripheral target tissues from inactive steroid precursors while in adult men approximately 50 of androgens are locally made in intracrine target tissues 4 . The major androgens that interact with the androgen receptor are testosterone and dihydrotestosterone. Androgen receptors have been localized to the basal layer of the sebaceous gland and the outer root sheath keratinocytes of the hair follicle 5, 6 . Dihydrotestosterone is approximately 5-10 times more potent than testosterone in its interaction with the androgen receptor. functional androgen receptor is required for sebum production. Since both testosterone and dihydrotestosterone act at this receptor, either one or both of these androgens is required to produce adult levels of sebum. 5a -Dihydrotestosterone 5a -Dihydrotestosterone Dihydrotestosterone is produced from...

Introductionacne Vulgaris

Although we know that hormones are important in the development of acne, many questions remain unanswered about the mechanism by which hormones exert their effects. For example, the specific hormones that are important in acne have not been definitively identified. Androgens such as dihydrotestosterone (DHT) and testosterone (T), the adrenal precursor dehydroepiandrosterone sulfate (DHEAS), estrogens such as estradiol and other hormones such as growth hormone may each be important in acne. It is not known if these hormones are taken up from the serum by the sebaceous gland or if they are made locally within the gland. Finally, the cellular and molecular mechanisms by which these hormones exert their influence on the sebaceous gland have not been fully elucidated. The goal of this chapter is to present the clinical and experimental evidence for the role of hormones in acne while pointing out gaps in our current understanding. As future research fills in these gaps, we will be able to...

Clinical Appearance Classification

Lupus Profundus

DLE lesions predominantly occur in the light-exposed areas of skin like face, ears, neck and arms, but may be found in sun-protected areas as well as inguinal folds, palmo-plantar locations and the scalp. At the latter location, DLE may even be the only cutaneous manifestation in 10 of cases and thus presents a classical differential diagnosis of scarring alopecia. Altogether involvement of the scalp can be found in about 60 of DLE patients (Sontheimer and Provost 1996) (Fig. 1C). With a distribution above the neck, the so-called localized form of DLE can be separated from a generalized DLE if it is present above and below the neck. Small, follicularly orientated erythematous papules of less than 1 cm in diameter present as follicular DLE at the elbows, but may occur at any other part of the body as well. Precipitation of DLE lesions by physical trauma (Kobner phenomenon) has already been mentioned above and may explain occurance at unusual locations. Fig. 1. A. Clinical presentation...

Hutchinson Gilford Progeria Syndrome

- Cutaneous changes include generalized lipodystrophy with a thin, atrophic, dry and inelastic skin, presenting with sclerodermatous focal lesions (Jansen and Romiti 2000) and hyperpigmented zones. Cutaneous appendices become atrophic, giving rise to alopecia and absence of eyebrows. The venous superficial network is prominent, mainly on skull and thorax

Cutaneous Manifestations

SCLE patients may also have LE nonspecific skin findings. The most common are diffuse alopecia, mucositis, livedo reticularis, periungual telangiec-tasias, small vessel vasculitis, Raynaud's phenomenon, cutaneous sclerosis (Sontheimer 1989), and red lunulae (Wollina et al. 1999). Dystrophic calcinosis cutis (Marzano et al. 1999), multiple HPV-11 cutaneous squamous cell carcinomas (Cohen et al. 1992), and erythema gyratum repens, a rare paraneoplastic eruption (Hochedez et al. 2001), have been case reported.

Parkinsonism Owing To Toxin Exposure

Several studies have explored the role of various environmental causes of parkinsonism, especially exposure to industrial toxins, organic solvents, pesticides, and other putative toxins (35,36). Population studies have shown a link between risk of PD, and chronic (more than 20 yr) exposure to manganese, lead-copper combinations, and iron-copper (37). Mercury exposure has also been linked to PD, but no firm evidence exists for mercury-induced parkinsonism. In the case-control study from Singapore, scalp hair mercury level has been shown to be a poor predictor of risk of PD (38).

Background 21 Cosmetic Procedures

Electrolysis and laser photothermolysis appear to be the most effective procedures, although with these methods hair removal should not be considered permanent. Moreover, multiple treatments are usually necessary because of the nature of the hair growth cycle. Electrolysis uses an electric current transmitted through a fine needle inserted into the hair follicle. This results in destruction of the follicle. There are different electrolysis techniques using direct (galvanic), high-frequency alternating current, or a combination (7). Pain is common, and scarring may occur if the operator is unskilled or if the current used is too high. Laser and light-assisted hair removal is based on the principle of selective photothermolysis. Selective absorption by hair chromophores of energy from lasers and broadband light sources may result in destruction of hair follicles while leaving the skin undamaged, although there are significant differences according to the specific characteristics of the...

Clinical Manifestations

Epidermolysis Bullosa Acquista

Classical EBA is a mechanobullous disease marked by skin fragility over trauma prone surfaces. Blisters, erosions and scars occur over the back of the hands, knuckles, elbows, knees, sacral area, and feet (Fig. 2A). There is often significant involvement of the oral mucosa with erosions and frank blisters. On the glabrous skin, the vesicles and bullae appear tense on non-inflamed or scarred skin. They can be hemorrhagic and can result in erosions, crusts, scales, scars, scarring alopecia, milia cysts and nail dystrophy. The lesions heal with scarring and frequently with the formation of pearl-like milia cysts within the scarred areas. In severe cases, there may be fibrosis of the hands and fingers and esophageal stenosis (Stewart et al. 1991 Harman et al. 1998). The histology shows dermal-epidermal separation at the BMZ and minimal inflammation.

Oligoadenylate synthetase 25OAS

O'Nyong-Nyong virus (ONNV) A species in the genus Alphavirus. The complete nucleotide sequence shows a close genetic relationship to Semliki Forest virus. In humans it causes a febrile illness with lymphadenitis, severe joint pains and rash. Epidemic spread occurs with anopheline mosquitoes as vector. Occurs in Uganda, Kenya, Tanzania, Malawi and Senegal. Pathogenic for suckling mice given i.c. older mice are resistant. Infant mice which survive the infection are stunted and show patchy alopecia. Virus is propagated in chick embryo fibroblast cell cultures.

Types and Distribution of Hair

Blood Capillaries Sweat Glands

Figure 6.8 Structure of a Hair and Its Follicle. (a) Anatomy of the follicle and associated structures. (b) Light micrograph of the base of a hair follicle. (c) Electron micrograph of two hairs emerging from their follicles. Note the exfoliating epidermal cells encircling the follicles like rose petals. Figure 6.8 Structure of a Hair and Its Follicle. (a) Anatomy of the follicle and associated structures. (b) Light micrograph of the base of a hair follicle. (c) Electron micrograph of two hairs emerging from their follicles. Note the exfoliating epidermal cells encircling the follicles like rose petals.

Clinical presentation

Impetigo is a superficial infection of the skin of which there are two forms. In the non-bullous form the affected skin is covered with crusts. Both staphylococci and streptococci are responsible. However the bullous form which presents with blisters is due to staphylococci. Folliculitis, an inflammation of the hair follicle, is commonly caused by Staph. aureus. Infection of the scalp or beard hair (sycosis barbae) is uncommon but may become chronic. Abscess formation around the hair follicles may result in furuncles or boils where several furuncles coalesce the lesion is known as a carbuncle.

Figure 328

It has been shown that regular pitting may convert to rippling or ridging, and these two conditions appear, at times, to be variants of uniform pitting (Figures 3.26-3.28). Nails showing diffuse pitting grow faster than the apparently normal nails in psoriasis. Occasional pits occur on normal nails. Deep pits can be attributed to psoriasis, and profuse pitting is most often due to this condition (Figures 3.29, 3.30). In alopecia areata (Figure 3.31) shallow pits are usually seen and they are often numerous, leading to trachyonychia (rough nail) and twenty-nail dystrophy however, curiously, one nail often remains unaffected for a long time, Pits may also occur in eczema or occupational trauma. In some cases a genetic basis is thought likely. In secondary syphilis and pityriasis rosea pitting occurs rarely. One case of the latter has been observed with the pits distributed on all the finger nails at corresponding levels, analogous to Beau's lines.

LH Genes and Genomes

Acids are arranged into units called genes, and the whole collection of genes constitutes the genome. Most genes are used as templates to produce proteins. The complement of proteins within a particular cell type is distinctive - a hair follicle will produce keratin and a pancreatic f-cell will produce insulin - but the protein content of a cell can also change dramatically depending upon, for example, the availability of nutrients. This means that in certain cell types, certain genes will be expressed and others will not, and the cell must have the ability to activate certain genes in response to external signals. This raises a number of issues. How is the cell able to discern within its genome what is a gene and what is not, and how is the cell able to turn a particular gene on while at the same time not affecting the expression of other genes

Local causes

Nail Disease Onychomadesis

The terms 'onychoptosis defluvium' or 'alopecia unguium' are sometimes used to describe traumatic nail loss. Onychomadesis usually results from serious generalized diseases, bullous dermatoses, drug reactions, intensive X-ray therapy, acute paronychia or severe psychological stress or it may be idiopathic. Nail shedding may be an inherited disorder (as a dominant trait) the shedding may be periodic, and rarely associated with the dental condition amelogenesis imperfecta. Longitudinal fissures, recurrent onychomadesis and onychogryphosis can be associated with mild degrees of keratosis punctata. Minor traumatic episodes (as in 'sportsman's toe') may cause onychomadesis of the toe nails (Figure 4.12).

Sebaceous Glands

Sebaceous32 (see-BAY-shus) glands produce an oily secretion called sebum (SEE-bum). They are flask-shaped, with short ducts that usually open into a hair follicle (fig. 6.11c), although some of them open directly onto the skin surface. These are holocrine glands with little visible lumen. Their secretion consists of broken-down cells that are replaced by mitosis at the base of the gland. Sebum keeps the skin and hair from becoming dry, brittle, and cracked. The sheen of well-brushed hair is due to sebum distributed by the hairbrush. Ironically, we go to great lengths to wash sebum from the skin, only to replace it with various skin creams and hand lotions made of little more than lanolin, which is sheep sebum.

Eflornithine

Eflornithine is an irreversible inhibitor of ornithine decarboxylase. This enzyme catalyzes the conversion of ornithine to polyamines, which are involved in the regulation of cell growth and differentiation in several tissues. The enzyme is modulated by androgens and takes part in the physiology of hair growth, regulating the proliferation of matrix cells in the hair follicle. Studies have indicated that blockade of this enzyme activity in hair follicles slows hair growth, and the drug has recently been licensed for topical treatment of facial hirsutism. Percutaneous absorption of the drug is negligible. In short-term clinical studies, eflornithine 11.5-15 cream was better than placebo in reducing hair growth in women with unwanted facial hair, as demonstrated by objective and subjective methods (11). However, hair growth returned to pretreatment rates within a few weeks after stopping treatment. Mild irritation and folliculitis may affect the skin with treatment. Anecdotal evidence...

Adduct

Agouti the grizzled color of the fur of mammals resulting from alternating bands of yellow (phaeo-melanin) and black (eumelanin) pigments in individual hairs. The name is also given to the genes that control the hair color patterns. In the mouse more than 20 alleles have been described at the agouti locus on chromosome 2. The gene encodes a cysteine-rich, 131 amino acid protein that instructs the me-lanocytes in the hair follicle when to switch from making black to yellow pigment. The protein is translated by nearby follicle cells rather than in the melanocytes themselves. Therefore, the agouti protein acts as a paracrine-signaling molecule. See Appendix C, 1905, Cuenot autocrine, MC1R gene, melanin.

Scalp and face

Scalp ringworm in children may be caused by anthropophilic fungi such as Trichophyton tonsurans, which is spreading in cities in the United Kingdom, or Microsporum audouinii. Sporadic cases are caused by M.canis which is acquired from cats or dogs. In all cases there is itching, hair loss, and some degree of inflammation which is worse with M. canis infections.

AInterferon

HBeAg, hepatitis B surface antigen (HbsAg), and HBV DNA should be monitored at the beginning of therapy, at the end of 16 weeks of therapy, as well as at 3 and 6 months after cessation of therapy, because some patients may become virologic responders after discontinuation of therapy. Patients who respond to therapy often develop a flare (transient increase in ALT 2 times baseline value) 8 to 12 weeks after initiation of therapy (59 of responders versus 35 of nonresponders). IFN can be continued during the flare unless signs of liver failure ensue patients should be monitored clinically and biochemically every 2 weeks during a flare. Adverse effects include flu-like symptoms, anxiety, depression, anorexia, weight loss, hair loss, bone marrow suppression, thyroid disorders, and auto-antibody induction.

Inhibition In Vivo

The therapeutic regression of primary tumors without toxicity has not been previously documented. In the studies with human AP, aggressive murine primary tumor growth was inhibited by 81-87 at doses of 50 mg kg given subcutaneously every 12 h, seen for the duration of the experiment of 60 d in some studies (8). There was no weight loss, bleeding, hair loss, growth abnormalities, or other toxicity in the treated animals, including those receiving 100 mg kg d, the maximum dose tested, of either human AP derived from elastase cleavage of plasminogen or recombinant human AP (8,15). It should be noted, however, that formal toxicity studies on AP have yet to be reported.

Seborrhea andor Acne

The prevalence of androgen excess among acneic-only patients (excluding patients with hirsutism) is less than among hirsute women. In small studies, between 20 and 40 of patients with treatment-resistant acne and without menstrual disturbance, alopecia, or hirsutism are reported to have androgen excess, principally PCOS (30-33). Alternatively, data regarding the predictive ability of seborrhea for androgen excess is lacking. Large populational studies of acneic or hyperseborrheic patients, particularly those without other evidence of hyperandrogenism (e.g., hirsutism), are then still needed to better define this prevalence.

Histopathology

The histopathologic features of LE specific skin disease include hyperkeratosis, epidermal atrophy, liquifactive vacuolar basal cell degeneration, and nodular perivascular and perifollicular mononuclear cell infiltrates. Some authors have reported degrees of LE specific features among LE subsets. SCLE has more epidermal atrophy, but less hyperkeratosis, basement membrane thickening, follicular plugging and inflammatory cell infiltrates when compared to DLE (Bangert et al. 1984 David-Bajar and Davis 1997). Since the histologic findings typically mirror the clinical findings, this is expected, and corresponds to the fine less adherent scale, lack of induration and less frequent alopecia of SCLE. Herrero et al biopsied the border of annular vesicular lesions in a SCLE cohort group with a high frequency of anti-Ro SSA and the HLA DR3 phenotype (Herrero et al. 1988). Epidermal necrolysis was prominent and the authors suggested this immunophenotype may correlate with the histologic...

Finasteride

Finasteride, strictly considered, is not an antiandrogen, in that it does not act at the androgen receptor. It is a competitive inhibitor of the type 2 isoenzyme of 5a-reductase, the enzyme responsible for conversion of testosterone to the more potent dihydrotestosterone. This drug has been approved for treatment of benign prostatic hyperplasia and male pattern baldness.

Behavioural control

Testosterone is the major hormone associated with the behavioural patterns exhibited by stallions. However, other hormones, such as dihydrotestosterone, do have a contributory effect. Both these hormones drive the normal libido of the stallion, possibly via their conversion to oestradiol and, through this, exert an effect on the higher centres of the brain (Johnson, 1991a). In addition to these two hormones, GnRH apparently directly affects behaviour, especially at the time of mating. At the sight of a mare, or at sexual stimulation, the frequency and amplitude of GnRH pulse release increase. The result is twofold an increase in LH and FSH pulse frequency and amplitude, leading to a rise in testosterone secretion and a corresponding enhancement of libido (Irvine and Alexander, 1991) and a direct effect on the higher centres of the brain, stimulating the CNS and so acting as an additional drive to mating behaviour (Pozor et al., 1991) (Fig. 3.26).

Endocrine Regulation

The prostate is dependent on testicular-derived testosterone despite the presence of the 3p-hydroxysteroid dehydrogenase-a5-a4 isomerase complex,160 the prostate has not been reported to synthesize testosterone de novo. It can reversibly metabolize testosterone to androstenedione (17P-hydroxysteroid dehydrogenase161) and, possibly irreversibly, to estrogens (see below). The prostate's primary metabolite of testosterone is dihydrotestosterone (DHT), an irreversible reaction catalyzed by 5 a-reductase.162 This is a more potent ligand for the androgen receptor than is testosterone, as it binds the receptor with greater affinity, enhances translocation from the cytoplasm to the nucleus, and is more effective in activating many androgen-response elements.163,164 Following 5 a-reduction, DHT and androstanedione are further metabolized by 3a p -hydroxysteroid dehydrogenase to 5 a-androstane-3a p-17P-diol and androsterone.165,166 The reader is referred to the work of Amann and colleagues167...

The epididymis

Cross Section The Epididymis

In order for maturation to occur, spermatozoa need to remain within the epididymis for up to 7 days. Those that are subsequently not ejaculated are reabsorbed, ensuring a continual supply of fresh spermatozoa (Gebauer et al., 1974a,b,c Thompson et al., 1979a). In general, mammalian epididymal fluid contains significant concentrations of glycerylphosphorylcholine, glycosidases, amino acids, androgen-dependent proteins, potassium, inositol, carnitine, dihydrotestosterone, and alkaline and acidic phosphatases. The specific concentration of these elements has not yet been ascertained in horses, but it is likely that equine epididymal fluid contains similar components (Rossdale and Ricketts, 1980 Setchell, 1991). Spermatozoa spend 4-5 days moving through the epididymis by means of muscle contraction of the epididymal walls and hydrostatic pressure. Spermatozoa can be stored in the caudal epididymis for between 2 days and several weeks. The storage capacity of the cauda is 10 X 109 storage...

Scabetic Lesion

Trichophyton Tonsurans Infection

This infant has neonatal tinea capitis (ringworm), which was diagnosed at the age of 3 weeks. The condition is rarely seen in the neonate. Lesions are sharply outlined and ring- or disc-shaped, and there may be confluent areas of alopecia with areas of broken and brittle hair observed on an erythematous, scaling scalp (silvery scales). The diagnosis of ringworm of the scalp can frequently be made by the presence of fluorescence under a Wood's light (the affected scalp appears green due to fluorescence of the infected hairs) or by microscopic examination of infected hairs. In the neonate, the infection is usually produced by Microsporon canis, M. audouinii, or Trichophyton tonsurans. The hair does not fluoresce in a Trychophyton tonsurans infection. (Levy, M., Moise, K.)

Testicular hormones

Testosterone Stallions

Dihydrotestosterone Dihydrotestosterone is a derivative of testosterone, produced in, and released from, the Leidig cells. Its function is likely to be as an additional negative feedback on pituitary function. It also has an effect on the development of male characteristics, but to a lesser extent than testosterone.

Babies With A Trach

Nager Acrofacial Dysostosis Syndrome

This infant with Nager's acrofacial dysostosis syndrome shows the slight antimon-goloid slant, prominent nose, malar hypoplasia, micrognathia, and atresia of the external auditory canal. Associated with the hypoplastic mandible may be a bony cleft of the mandibular sym-physis. In addition, the infant had radial hypoplasia and absence of thumbs. This infant required an emergency tracheostomy. Also note the projection of the scalp hair onto the lateral cheek. Figure 3.108. This infant with Nager's acrofacial dysostosis syndrome shows the slight antimon-goloid slant, prominent nose, malar hypoplasia, micrognathia, and atresia of the external auditory canal. Associated with the hypoplastic mandible may be a bony cleft of the mandibular sym-physis. In addition, the infant had radial hypoplasia and absence of thumbs. This infant required an emergency tracheostomy. Also note the projection of the scalp hair onto the lateral cheek.

Ovarian Sonography

Clinical experience has indicated that the majority of women with signs of virilization (i.e., mas-culinization of body muscular, severe or extreme male-pattern balding or hirsutism, clitoromegaly, etc.) will have androgen excess. Although rarely a sign of PCOS, virilization can be seen in patients with disorders of severe insulin resistance, androgen-secreting tumors, and androgenic substance abuse. Less clear is the predictive ability of less dramatic signs and symptoms. Although reviewed previously (see Chapter 14), it is still noteworthy to briefly summarize the predictive ability of the various historical and clinical features of androgen excess.

Functions of Hair

Tufts and patches of hair, sometimes with contrasting colors, are important among mammals in advertising species, age, sex, and individual identity. For the less groomed members of the human species, scalp hair may play a similar role. The indefinitely growing hair of a man's scalp and beard, for example, could provide a striking contrast to a face that is otherwise almost hairless. It creates a badge of recognition instantly visible at a distance.

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