Lecture 6 Part 2 PDF

Hyperhidrosis Hyperhidrosis affects up to several percent of the population. The major areas affected by hyperhidrosis are the palms, soles, and axillae. In some cases, only the palms and/or soles are involved. In other cases, only the axillae are involved, and in other cases, all three areas may...

Hyperhidrosis Hyperhidrosis affects up to several percent of the population. The major areas affected by hyperhidrosis are the palms, soles, and axillae. In some cases, only the palms and/or soles are involved. In other cases, only the axillae are involved, and in other cases, all three areas may be involved. There are two main temporal patterns of hyperhidrosis. In one group of patients, the hyperhidrosis is only present with emotional stress (anxiety) – these patients tend to have predominant palm/sole involvement. In the other group, the hyperhidrosis is essentially continuous – these patients tend to have predominant axillary involvement. Sweating of the palms and soles is controlled by the cerebral cortex. In a normal response to stress, these areas sweat slightly, providing improved grip. They do not normally sweat in response to increased core body temperature. Sweating of the axillae is controlled both by cortical and hypothalamic centers. The axillae sweat in response to both emotional stimuli and increased core body temperature. Sweating of the rest of the body is controlled by hypothalamic centers, and increased sweating happens in response to increased core body temperature. In patients with predominantly emotional hyperhidrosis, there is overactivity of the cortical centers controlling this type of sweating. In patients with continuous axillary hyperhidrosis, there is overactivity of the hypothalamic centers controlling axillary sweating. First line treatment for hyperhidrosis is aluminum chloride. This substance forms a plug in the eccrine ducts, thereby stopping eccrine sweat release. If 25% aluminum chloride is not effective, referral to a dermatologist for consideration of surgical techniques, anti-cholinergic medications, and electrical stimulation is appropriate. For patients with anxiety related hyperhidrosis, anxiolytic medications or psychological intervention to decrease anxiety may be beneficial. Hyperhidrosis is also very rarely associated with neurologic disease, spinal cord injuries, nerve damage, and endocrine disorders. Keloids and Hypertrophic Scars Keloids and hypertrophic scars are quite common. Keloids are much more common in African- Americans, while hypertrophic scars are relatively equally common between races. Neither entity demonstrates an overwhelming male or female predominance. Keloids and hypertrophic scars are both examples of excessive scar formation. Common features include being raised, tender, and erythematous early in their course, and remaining raised permanently. The erythema and tenderness resolve as the lesions mature. The two lesions differ because a keloid extends laterally beyond the borders of the initial wound (Figure 6.26) (Figure 6.27), while a hypertrophic scar remains within the borders of the original wound (Figure 6.28). Both differ from a typical scar by being more raised and firm than what is expected for a typical scar. Both lesions have strong familial components. In addition, certain body areas are at significantly greater risk for developing these lesions. Areas at particular risk include the earlobes and the central chest, especially directly overlying the sternum. In addition to family history and location, the nature of the initial wound affects the likelihood of developing a keloid or hypertrophic scar. Inflammation, infection, foreign bodies, and tension all increase the probability of keloid/hypertrophic scar development. The pathogenesis of these lesions is poorly understood. However, the best current hypothesis is that excessive transforming growth factor beta (TGF-β) activity is the most likely cause. This cytokine stimulates production of extracellular matrix components. There are several treatment options. In general, hypertrophic scars are much more responsive to treatment than are keloids, but the same types of treatments are used for both. The simplest approach is massage therapy, in which the patient firmly massages the lesion for 5-10 minutes 3- 4 times per day. This should be started approximately 6 weeks after the wound initially heals. A lubricant, such as Vaseline, shea butter, or vitamin E, assists in the massage, but it does not matter which lubricant is used. Other treatment options include intralesional steroid injections, surgery to excise the lesion coupled with intralesional steroid injections at the time of surgery to prevent recurrence, and several experimental topical therapies. Striae Distensae (Stretch Marks) Striae are quite common, affecting up to ¼ of individuals during puberty, and up to ¾ of women during pregnancy. They are associated with rapid weight gain in a specific area. Striae present as pink-to-red-to-purple linear depressions. Over time (usually about 1 year) the color fades, leaving a linear depression. They are typically asymptomatic, although they do itch mildly in some patients. In males during puberty, common locations are the thighs (Figure 6.29), lower back, and upper back/shoulders. In females during puberty the breasts, thighs, and buttocks are most common. Obviously, in pregnant women, the abdomen is most commonly affected. Striae can be indicators of pathologic states, such as Cushing’s disease or topical steroid overuse. Tip offs that striae are indicative of pathologic states include striae in unusual locations and striae developing during times other than puberty or pregnancy. Striae develop when the tension on the skin exceeds the tensile strength of the dermis. This can happen if there is excessive tension on normal skin (most situations) or if there is normal tension on skin with abnormally low tensile strength (Cushing’s disease, excessive topical steroid use). Other than decreasing the rate and extent of weight gain, there is no known way to prevent striae. Treatment is disappointing, but retinoids have been shown to have some benefit. Some types of lasers can help speed normalization of the color of lesions. Oral and Genital HSV The prevalence of HSV-1 antibodies (indicating infection) is 80-90% and 15-25% for HSV-2 antibodies. 80% of cases of oro-labial herpes are due to HSV-1, and 20% are due to HSV-2. Conversely, 80% of cases of genital herpes are due to HSV-2, and 20% are due to HSV-1. Classic symptomatic outbreaks of herpes are manifested initially by pain, burning, and tingling prior to appearance of lesions. Lesions are localized groups of vesicles on erythematous bases (Figure 6.30) (Figure 6.31). After the vesicles rupture, a painful superficial ulcer often remains. On the genitals the patient may not notice the vesicles, so herpes always needs to be suspected if a patient presents with a painful genital ulcer (Figure 6.32). However, many cases, especially genital cases, are atypical. In fact, in some studies, the majority of individuals with genital herpes have asymptomatic disease, and they are unaware that they have the disease until a positive serologic study is obtained. After the initial contact, the virus replicates in the mucocutaneous tissue, then travels up the axon and establishes latency in the dorsal root ganglion. Stress, immunosuppression, ultraviolet light, and trauma can all stimulate viral activation, although most viral re-activations are spontaneous with no obvious inciting factor. The initial infection is typically the most severe outbreak, and systemic symptoms can be seen with primary infection. Virus is typically spread by contact with contaminated fluids or secretions (saliva, blister fluid, etc). There is also a high incidence of asymptomatic viral shedding, in which infective viral particles are being shed from the skin or mucous membrane in the absence of clinical lesions or symptoms. Eczema Herpeticum or Kaposi’s varicelliform eruption is a rare syndrome in which HSV disseminates widely in the skin of an individual with compromised skin barrier function. The classic scenario is a young child with atopic dermatitis who is kissed by an adult with a cold sore (Figure 6.33). Finally, a localized herpetic infection on the finger is called a herpetic whitlow (Figure 6.34). This historically occurred in dental workers from contact with patients with oral HSV. Herpetic whitlow has become much less common since universal glove use has taken hold. Herpes viruses are double stranded DNA viruses. HSV-1 and HSV-2 are generally spread by direct skin-to-skin contact. HSV-1 and HSV-2 are treated with oral or IV antiviral agents. Most commonly used are acyclovir and valacyclovir. Valacyclovir is a prodrug of acyclovir, and the advantage of valacyclovir is that it has dramatically better oral bio-availability. These agents are nucleoside analogs that derive their specificity for virally infected cells from the fact that they are dependent on viral thymidine kinase for activation. Treatment can be either episodic or prophylactic. In episodic treatment, antiviral medication is started as soon as possible, preferably at the first sign of an outbreak. This can dramatically accelerate resolution of a given outbreak. In prophylactic treatment, low dose antiviral medication is taken daily, with the intent of preventing outbreaks. In addition to preventing symptomatic disease, prophylactic treatment dramatically decreases asymptomatic viral shedding, and therefore decreases infectivity. Studies have shown that if one sexual partner is infected with HSV-2 and the other partner is not infected, prophylactic treatment of the infected partner decreases the probability that the uninfected partner will contract the disease. Erythema Migrans Erythema migrans is the specific cutaneous manifestation of Lyme disease. It is most common in individuals who have recently been to an endemic area. Erythema migrans presents as an expanding, red plaque. The central area often clears as the plaque expands peripherally (Figure 6.35). It is usually asymptomatic. It usually appears from two days to two weeks after the tick bite, and untreated it resolves in approximately one month. 50-75% of patients with Lyme disease will have erythema migrans. Erythema migrans is the major manifestation of the primary stage of Lyme disease. There are no specific cutaneous manifestations of the second or third stages. Lyme disease is caused by the spirochete Borrelia burgdorferi. The spirochete is transmitted by the bite of ticks of the Ixodes species: I. pacificus in the western United States and I. scapularis in the eastern United States. Borrelia can be transmitted to the patient when the tick bites and remains attached to the skin for at least 24 hours. If the duration of attachment is less than 24 hours, transmission is very unlikely. Lyme disease is treated with doxycycline. Diagnosis is confirmed with ELISA and Western blot. Erythema Multiforme (EM) EM is a self-limited reactive disorder. By far the most common underlying disease is herpes simplex. EM is rare in young children and in individuals beyond their 40s. EM presents as red papules that develop into “target” lesions. The target’s center is usually a blister or scab, surrounded by a pale, edematous area. Surrounding this area is a red halo. Some lesions may not have the classic target appearance and may simply look like red papules. In fact, some patients may not have any true target lesions, and may only have red papules and blisters. EM most commonly involves the dorsal hands and forearms. Other areas that may be involved include the chest, palms, and legs (Figure 6.36) (Figure 6.37), or the oral mucosa (Figure 6.38). About half of patients have a clinically apparent outbreak of oral or genital HSV preceding the EM eruption. The other half have either subclinical HSV outbreaks, other infections (mycoplasma, histoplasmosis, EBV), or have idiopathic EM. When there is a preceding HSV eruption, the EM typically follows it by several days to two weeks. EM likely represents an immune reaction to antigens from inciting infectious agents deposited in the skin. In other words, in HSV related cases, HSV antigens probably end up being deposited in the skin, and an immune reaction to these antigens clinically manifests as EM. Once EM appears, symptomatic treatment with antihistamines and NSAIDs is most effective. Early treatment of HSV outbreaks may help decrease the likelihood of an EM attack and may decrease its duration and severity, if an attack occurs. For patients with recurrent EM outbreaks, suppressive therapy with valacyclovir to prevent HSV outbreaks can prevent the EM outbreaks. Genital Warts Genital warts are probably the most common sexually transmitted disease. They are generally transmitted by direct contact. HPV types 6 and 11 are most common. Genital warts appear as verrucous papules on the genitalia or in the genital area. They are typically slightly hypo- or hyperpigmented (Figure 6.39). The surface is rough and “pebbly” (Figure 6.40). The dilated capillary loops often visible in cutaneous warts as dark dots deep in the wart are usually not visible in genital warts. Common areas besides the penis are perianal (Figure 6.41) (Figure 6.42) and vulvar (Figure 6.43). Individuals with suppressed cell-mediated immunity are at particular risk for developing genital or anal carcinoma associated with genital or perianal warts. Examples are organ transplant recipients and individuals with HIV infection and low CD4 counts. These patients should be referred to GI surgeons for monitoring with anoscopy for anal canal warts and carcinoma. Finally, genital warts in children are a controversial topic. In very young children (less than three years old), they are very unlikely to be a sign of sexual abuse. In children older than three years old, most cases are not due to sexual abuse, but the risk is higher. Most children are thought to get genital warts by touching their own genital area or by vertical transmission from the mother during birth. Genital warts are most important because of their association with cervical carcinoma in women and anal carcinoma in individuals with perianal warts (this risk is especially high in individuals who contract perianal warts through receptive anal intercourse). Most genital and perianal warts (and most warts in general) will spontaneously resolve, and HPV DNA may no longer be detectable following spontaneous resolution. However, since multiple studies have demonstrated the presence of HPV DNA in clinically-normal appearing skin, if clinical lesions resolve, it is impossible to tell based on exam if the infection is truly gone, or if the virus has simply gone into a latent, subclinical state. For this reason, it is safest to assume that any patient who has had a genital wart is at lifelong risk for recurrence, and is potentially shedding virus at all times. Treatment modalities can be divided into destructive therapies and immunity based therapies. Destructive therapies seek to destroy tissue with active HPV infection. Examples include cryotherapy, laser destruction, electrodessication, surgery, acid application, and podophylotoxin application. Immunity based therapies seek to initiate an immune response against the virus. The main immunity based therapy currently is a topical medication called imiquimod. This agent activates toll-like receptor 7 and thereby stimulates localized cytokine production, which helps incite an immune response. Intralesional interferon injections have also been used, and work via a similar mechanism of action. The major advantage of immunity based therapies is that when they are successful, there is a reasonable possibility that a long-lived specific immune response with develop to prevent recurrence. The major advantage of destructive techniques is that immediate destruction of clinical lesions is achieved. Counseling is just as important as treatment for all patients: 1) They can definitely spread the infection while they have active lesions, and they may be able to spread the infection even when there are no visible warts. 2) Women with a history of genital warts should have yearly pap smears to facilitate early detection of cervical cancer. 3) Men with genital warts should warn all sexual partners to be screened for infection. 4) Individuals with perianal warts and a history of receptive anal intercourse should have anoscopy to look for evidence of proximal HPV infection of the anal canal, which is a significant risk factor for anal carcinoma. Plantar Warts Plantar warts are exceedingly common. The most common areas are the ball of the foot and the heel area (Figure 6.44). These warts are often painful. The most reliable ways to differentiate plantar warts from calluses and corns are 1) the interruption of skin lines present in warts, and 2) the deep, red-black dots in a wart secondary to capillary hemorrhage. Some cases can be quite severe (Figure 6.45). Treatment usually must be multimodal. Chemical or physical debridement of the overlying keratotic skin is necessary to allow other therapies to penetrate to the area of active infection. Chemical debridement is most often done with salicylic acid liquid or adhesive. Physical debridement is usually done with a scalpel in the doctor’s office. Once debridement has been achieved, medications designed to inhibit HPV proliferation (5-fluorouracil) or incite an immune response (imiquimod) are employed. Pulsed Dye Laser treatment is also effective. Tinea Versicolor (TV) TV is very common. It most commonly presents in the summer and fall. Individuals of Mediterranean descent are most commonly affected. TV usually presents as hypo- or hyper-pigmented macules with very fine scale (Figure 6.46). In lightly pigmented individuals, the patches will often have a slight, reddish brown color (Figure 6.47). The lesions are almost always asymptomatic. The rash is typically distributed on the upper chest, upper back, and shoulders, although other areas may be affected. TV is caused by an overgrowth of yeast (Pityrosporum ovale), which is present at a low level on the skin of most individuals. This organism thrives on lipids, such as sebum. This is part of the reason it is more common in the late summer and fall. Patients frequently present with hypopigmented macules. The hypopigmentation is due to dicarboxylic acids produced by the yeast. These acids inhibit melanin formation. This is the other factor leading to patient’s presenting in the late summer – the hypopigmented lesions are more apparent when the surrounding skin is tanned. Treatment of TV is directed at preventing overgrowth of the yeast using anti-yeast agents. Ketoconazole shampoo to the affected areas is the most common treatment. Other options include antifungal creams (ketoconazole, econazole, miconazole, etc.). Allylamines (terbinafine, butenafine) should be avoided, as they have poor TV coverage. In severe cases, a single dose of either oral ketoconazole or oral fluconazole, repeated weekly for 2-4 weeks is very effective. It is important to counsel a patient that after the fungal overgrowth is cured, it will still take several months for the pigmentation to return to normal. Pediculosis Pubis (Crab Lice) P. pubis is caused by the crab louse (Phthirus pubis). It is relatively uncommon, and it most commonly affects sexually-active individuals in the teenage years through the thirties. The disease most commonly presents with severe pruritus in the genital region. Any other hair- bearing areas, especially the eyelashes, may rarely be involved. The lice are barely visible to the naked eye and may be difficult to see on clinical exam (Figure 6.48). Affected areas typically show perifollicular erythema and excoriations. In severe infections, there may be localized lymphadenopathy. Phthirus pubis is a louse with a short, wide body. It has claw-shaped legs that allow it to grip hairs very strongly. Treatment of localized infection is with topical insecticides, most commonly permethrin 5% cream left on overnight. The permethrin kills live lice, but does not kill eggs. Therefore, after treatment viable eggs remain, and these eggs hatch over the next several days. Retreatment one week after the first treatment kills these newly hatched lice before they can lay more eggs. In widespread cases or cases involving the eyelashes (where permethrin can’t be applied) oral ivermectin (another insecticide) is effective. In this case, the lice ingest the insecticide with their next blood meal. Treatment with oral ivermectin must be repeated one week after the first treatment, for the same reason noted above.