Lecture 6 - Teenage and 20s PDF

Lecture 6 – Teenage and 20s Moles (Melanocytic Nevi) Moles are extremely common. Most people have at least one mole. Individuals with many moles are not uncommon. This is a familial trait. In addition, having many atypical moles is a separate familial trait and is associated with an increased risk...

Lecture 6 – Teenage and 20s Moles (Melanocytic Nevi) Moles are extremely common. Most people have at least one mole. Individuals with many moles are not uncommon. This is a familial trait. In addition, having many atypical moles is a separate familial trait and is associated with an increased risk of melanoma. The term mole and nevus will be used synonymously throughout this lecture. Moles come in four major types: junctional, compound, dermal, and atypical. It is thought that the natural history of a typical mole is to start as a junctional nevus, progress through being a compound nevus, and end up as a dermal nevus. This progression happens over decades. Junctional nevi are thus named because melanocytes proliferate at the junction between the epidermis and dermis. These moles are flat and brown (Figure 6.1) (Figure 6.2). Looking at them with the naked eye, it is difficult to separate them from freckles or lentigines. Compound nevi have proliferations of melanocytes both at the junction between the epidermis and dermis and in the dermis. These moles are raised and brown (Figure 6.3) (Figure 6.4). Dermal nevi have proliferations of melanocytes strictly in the dermis. These moles are raised and skin colored (Figure 6.5). As can be seen by the above descriptions, the proliferation of melanocytes starts superficially, and progresses deeper into the skin over time. Atypical nevi usually have proliferations of melanocytes at the dermal-epidermal junction and in the dermis. These nevi differ from compound nevi in both clinical and histological appearance. Clinically, atypical nevi can have one or several of the following features that distinguish them from regular compound nevi: Irregular borders and irregular shape: Typical nevi are round or oval shaped and symmetrical, with smooth, sharp, consistent borders. Atypical nevi may have irregularities in shape, and their borders may be “blurred” or “fuzzy”. Irregular color: Typical nevi are one color (the color may vary from nevus to nevus, but in a given nevus, the whole nevus is the same color). The color is brown and homogenous throughout. Occasionally, there are two different tones of brown in a typical nevus. An atypical nevus will have at least two different tones of brown, and may have other colors as well – gray, blue, pink, white, black. Atypical nevi are often said to have a “fried egg” appearance: raised, darker center with flat, lighter colored periphery. Size: Atypical nevi tend to be larger than typical nevi. Most typical nevi are 50% of the population is affected with no effect on overall health, it has been argued (generally unsuccessfully) that having acne is the normal physiologic state. It typically starts with puberty, although in some patients, onset of acne can occur with adrenarche, preceding other clinical signs of puberty. Acne persists into adulthood very frequently, especially in women. For women in whom acne persists into the mid-twenties and beyond, it is almost always related to abnormal cutaneous responsiveness to androgenic hormones. There is a familial component. However, family history is a better predictor of severity of acne rather than presence of acne. Acne involves 3 main areas: face, chest, and back/shoulders. Involvement of the chest and back generally signals more severe disease. Involvement of the chin and/or jaw line in women generally signals hormonally-driven acne. There are six distinct lesions in acne: open comedone, closed comedone, papule, pustule, nodule, scar In a given patient, one type of lesion may exist exclusively, one or two types of lesions may predominate, or all six types of lesions may be present. Non-Inflammatory: Open Comedone (blackhead): dilated pore filled with dark material (Figure 6.15) Closed Comedone (whitehead): small (1-2 mm) flesh colored papule (Figure 6.16) Inflammatory: Papule: red papule, no deep component (Figure 6.17) Pustule (whitehead): white pustule on a red base, no deep component (Figure 6.18) Nodule: large (0.5 – 2 cm), red, tender nodule with deep component. Individual lesion may persist for weeks. Occasionally called “cysts”, but this term should be avoided. (Figure 6.19) Scars: Raised: Flesh colored to pink, dome shaped, firm papule  Depressed: Ice pick: Narrow, deep depression – most common (Figure 6.20) Valley: Wide, shallow depression Box Car: Wide, deep depression The pathogenesis of acne begins with abnormal cohesiveness of the keratinocytes at the openings of hair follicles. These abnormally cohesive keratinocytes form a plug in the follicle. As described in lecture 1, the sebaceous gland empties into the hair follicle; therefore, the plug in the opening leads to accumulation of sebaceous secretions within the follicle. The lesion is not visible to the naked eye and is called a microcomedone. At this point, the lesion is at a crossroad, and the microcomedone develops into one of the clinical acne lesions. Without an inflammatory stimulus, either an open or closed comedone will develop. In each of these lesions, the accumulation of sebaceous material enlarges the follicle, compressing the neighboring sebaceous gland, and leading to cessation of sebaceous production. The lesion is then static, and will remain quiescent for an indefinite period of time. Of note, a common myth is that the dark color of an open comedone (blackhead) is due to dirt. This is incorrect. The dark color is actually due to oxidized sebaceous material, and dirt plays no role. With an inflammatory stimulus, the microcomedone will develop into one of the inflammatory lesions. If the inflammation develops in the superficial portion of the follicle, a pustule will form. If the inflammation develops in the deep portion of the follicle, a papule will form. If a pustule ruptures spontaneously (or is squeezed) the follicular contents are extruded to the skin surface, and the lesion resolves relatively quickly. If a papule ruptures spontaneously (or is squeezed) the contents are released into the dermis, inciting a massive inflammatory response, leading to formation of a nodule. Nodules have the potential to form scars. The source of inflammatory stimuli is Propionibacterium acnes. These anaerobic, gram-positive rods produce lipases which degrade sebaceous secretions. The degradation products are pro- inflammatory, and in addition, several pro-inflammatory cytokines are also produced. P. acnes requires a high lipid environment for optimal growth. Androgenic hormonal influences are acnegenic in several ways. Most importantly, sebaceous glands increase secretion significantly as a result of androgenic stimulation. This increased production of sebum provides a much better environment for P. acnes proliferation. In addition, either through direct effect on keratinocytes or as a secondary effect from the increased sebum, androgenic hormones promote follicular plugging. Treatment of acne is directed at the underlying pathogenesis. In patients with predominantly open and closed comedones treatment is directed at abnormal keratinocyte cohesion. Retinoids, such as tretinoin or adapalene, are the most effective topical medications for decreasing keratinocyte cohesion. Salicylic acid is another effective topical medication for this purpose. For patients with inflammatory lesions, treatment is directed at keratinocyte cohesion, P. acnes overgrowth, and inflammation. Retinoids are used to address keratinocyte cohesion. Topical antibiotics, such as clindamycin and benzoyl peroxide, are used to decrease P. acnes populations. Finally, oral antibiotics, such as doxycycline, are used to decrease P. acnes counts and for their non-specific anti-inflammatory activity. Several antibacterial washes also decrease P. acnes counts. For patients with severe disease, an oral retinoid, isotretinoin (Accutane) is used. Isotretinoin is the only medication capable of directly decreasing sebaceous gland activity, and this decrease is permanent. The decrease is greatest while the patient is on isotretinoin, and there is a return towards baseline activity after isotretinoin is stopped, but the activity never returns to baseline. In addition, isotretinoin decreases keratinocyte cohesion, which is also probably permanent. Isotretinoin is dosed based on weight, and is typically given for a five to six month treatment course. 70 – 80% of patients will be “cured” of their acne after a course of isotretinoin. Finally, in women with acne around the chin or along the jawline, or in whom a monthly cycle to their acne severity occurs, therapy designed to decrease androgenic influence on the skin is appropriate. The two choices are either an oral contraceptive or spironolactone. Oral contraceptives must be chosen carefully. Most OCPs have an estrogenic component and a progestin component. Most progestins have androgenic activity, but some synthetic progestins have very low androgenic activity (norethindrone, levonorgestrel), and one is anti-androgenic (drospirenone), and these agents are effective for acne. The effectiveness of isotretinoin was already discussed. Other regimens are also quite effective. When the treatment regimen is appropriately matched to the type of acne, in general we expect an 80% improvement in acne over an 8-12 week period. One of the most important factors in acne treatment is compliance. Compliance is actually very low and is the most common cause of treatment failure. Most topical regimens can be irritating, especially when they include a retinoid, and this should be discussed with patients. If irritation develops, the patient should suspend therapy until the irritation resolves, then restart therapy, but only apply the medications every other day. Pityriasis Rosea (PR) Pityriasis rosea is most common in teenagers, but it is not infrequent in children or young adults. In over half of cases, pityriasis rosea starts with a “herald patch”, an oval, red to brown plaque with peripheral scale measuring from 2 - 10 cm in diameter (Figure 6.21). The herald patch is usually on the trunk. Within days to a week after the herald patch appears, similar appearing but smaller plaques appear, distributed widely across the trunk (Figure 6.22). In cases without a herald patch, the widespread eruption is the first manifestation of the disease. These patches are predominantly on the trunk and proximal extremities. Most patients are asymptomatic, but a significant minority experience some itch. The distribution and arrangement of the plaques are very distinctive. The long axes of the oval plaques are oriented in a “Christmas Tree” distribution over the trunk. (Figure 6.23) Pityriasis rosea is probably caused by human herpesviruses 6 and 7 (HHV-6 and HHV-7). This is the prevailing theory, supported by epidemiology and by identification of viral DNA in many patients. However, definite evidence of the etiologic role of these viruses is lacking. In most cases, PR will resolve spontaneously in 6-8 weeks, although rare cases will persist for up to 6 months. Topical steroids can be used for treating associated pruritus. Keratosis Pilaris (KP) KP is extremely common. It is associated with atopic dermatitis, asthma, and hay fever. KP presents as rough, red papules at hair follicle openings (Figure 6.24). It is most commonly present on the dorsal aspects of the upper arms. The other common location is the anterior thighs. One of the most reproducible findings in KP is the rough feel of affected arms and legs. Keratosis pilaris is treated with keratolytic moisturizers, such as ammonium lactate (Am-Lactin) or urea, or with retinoids (tretinoin). Acanthosis Nigricans (AN) Acanthosis nigricans is common in overweight individuals and individuals with abnormal glucose tolerance. AN presents as darkening of the skin around the neck, in the axillae, in the antecubital fossae, and over the knuckles of the fingers/toes. In addition to the darkening of the skin, there is also thickening of the skin, giving it a “velvety” texture (Figure 6.25). AN is poorly understood. One of the theories of the cause of darkening and thickening is a cutaneous response to activation of the insulin-like growth factor receptor. Another theory is that the darkening and thickening is a response to friction. Both theories are largely in response to the obvious association between AN and obesity, glucose intolerance and hyperinsulinemia. Acanthosis nigricans is difficult to treat. In obese individuals, weight loss is essentially the only treatment likely to be effective. The most difficult question to answer when evaluating a patient with AN is how aggressively to evaluate them for underlying causes. The vast majority have no detectable underlying abnormality. In most patients, it is worth checking fasting blood glucose to rule out frank diabetes, and in patients with a family history of diabetes, it is worth considering referring them to endocrinology for evaluation for abnormal glucose tolerance and/or hyperinsulinemia in the absence of frank diabetes. In extremely rare cases, AN can be associated with underlying malignancies. Classically, gastric adenocarcinoma is the most common, although many different tumors have been reported. In these cases, it is thought that the tumor is producing a substance that binds to and activates the insulin-like growth factor receptor. If a patient presents with rapidly developing and progressing AN, especially involving the peri-oral area, they should be aggressively evaluated for underlying malignancies.