Lecture 7 - 20s and 30s PDF

Lecture 7 – 20s and 30s Psoriasis Psoriasis affects 1-3% of the US population, equally affecting males and females. It is relatively more prevalent among Caucasians and relatively less prevalent among African-Americans, Africans, Asians, and Native Americans. Incidence is highest in the 20s. There...

Lecture 7 – 20s and 30s Psoriasis Psoriasis affects 1-3% of the US population, equally affecting males and females. It is relatively more prevalent among Caucasians and relatively less prevalent among African-Americans, Africans, Asians, and Native Americans. Incidence is highest in the 20s. There is a second, smaller peak around age 60. Onset has been reported from birth to over age 100. Onset in childhood is a risk factor for worse disease. Psoriasis does have a heritable component. About 1/3 of patients with psoriasis have at least one affected relative. 65% of monozygotic twins are concordant for the disease. If one parent has psoriasis, there is about a 10% chance that a given child will have psoriasis. If both parents are affected, the chance jumps to 40%. There are several types of psoriasis: The most common type is chronic plaque psoriasis. Other types include guttate psoriasis, pustular psoriasis, inverse psoriasis, erythrodermic psoriasis, nail psoriasis, and psoriatic arthritis. A given patient may manifest more than one type at any given time, and they may change from one type to another over time. Chronic plaque psoriasis is manifested by sharply-bordered, red plaques with adherent silvery scale (Figure 7.1) (Figure 7.2) (Figure 7.3) (Figure 7.4). The plaques usually itch. Common locations are the elbows, knees, scalp, buttocks, and umbilicus, although anywhere may be affected. Most patients have less than 5% of the body covered, but up to 90% of the body may be covered. The disease is considered “moderate to severe” when ≥10% of the body is covered. Guttate psoriasis is manifested by one to hundreds of small (1-2 cm) plaques that have the same morphology as the plaques in chronic plaque type (Figure 7.5) (Figure 7.6) (Figure 7.7) (Figure 7.8). This type is most common in children, although it often happens in adults as well. It often follows a streptococcal infection, and may or may not resolve after the strep infection resolves. It most commonly involves the trunk. It can be difficult to distinguish from pitryriasis rosea. The two most useful ways to tell them apart are to look for the herald patch and/or the “Christmas tree” distribution of PR on history and on exam. Pustular psoriasis may be localized or generalized. The localized disease affects the hands and feet, predominantly the palms and soles. Small pustules on red bases develop. They are typically present in different stages, so that there will be some fresh, red pustules and some older, brown, dried-up pustules (Figure 7.9). The generalized disease is called “Pustular psoriasis of Von Zumbusch”. It can have an acute onset or slowly develop from other types of psoriasis. Patients present with widespread erythema and innumerable pustules (Figure 7.10) (Figure 7.11) (Figure 7.12). They are quite sick, with fevers, hypocalcemia, and other electrolyte abnormalities. They typically require ICU admission, and this disease is occasionally fatal. Pustular psoriasis of Von Zumbusch is often precipitated by discontinuing treatment with systemic steroids in a patient with pre-existing psoriasis. This is why patients with psoriasis should never be treated with systemic steroids except under the close supervision of an experienced dermatologist. Inverse psoriasis affects the body folds (axillae, groin, inter-gluteal cleft, inframammary areas, and retro-auricular folds). Moist, red plaques with sharp borders and little scale are the typical findings (Figure 7.13) (Figure 7.14). It is often confused with fungal infections, and it should only be diagnosed if a KOH scraping is performed and is negative. Erythrodermic psoriasis is psoriasis affecting over 90% of the cutaneous surface. It may develop suddenly in patients with no history of psoriasis or it may develop slowly from other types of psoriasis. It may be pustular or plaque type (Figure 7.15). It is very difficult to differentiate this rash from other causes of total body rash. Patients can have difficulty with temperature regulation, high output cardiac failure, and hypoalbuminemia. Nail psoriasis may be an isolated finding or may occur in patients with other types of psoriasis. Findings include nail pits (Figure 7.16) (Figure 7.17), yellow discoloration of the nails (Figure 7.18), separation of the nail from the nail bed, and collection of debris under the nail. From one nail to all 20 nails may be affected. Nail psoriasis is a risk factor for psoriatic arthritis. Nail changes can be useful to confirm a diagnosis of psoriasis in patients with unusual types of psoriasis. Nail psoriasis can closely mimic onychomycosis (nail fungus). Psoriatic arthritis occurs in up to one third of patients with psoriasis. There are five types: The most common is an asymmetric oligoarthritis (affecting several scattered joints, most commonly in the hands and feet). Other types are: symmetric arthritis of the small joints of the hands and feet (very similar to rheumatoid arthritis), asymmetric arthritis of the distal interphalangeal (DIP) joints, arthritis mutilans of the phalanges and metacarpals (pencil in cup deformity on x-ray), and ankylosing spondylitis. It is possible to have psoriatic arthritis without skin manifestations of psoriasis, but this is very difficult to diagnose. Auspitz sign is the appearance of drops of blood after gently removing a scale from a psoriatic lesion. Koebner phenomenon is the development of a psoriatic plaque at the site of trauma to the skin. Examples of trauma include burns, scratches, and blunt trauma. In general, there are several known exacerbating factors for psoriasis. Best known are cold weather and lack of sunlight (i.e., Pittsburgh). We see a clear overall worsening of our psoriatic patients through the fall and winter. Stress also worsens psoriasis. Smoking, obesity, diabetes, and alcoholism are all associated with psoriasis, although these epidemiologic connections are still being worked out. The course of the disease is chronic, with remissions and exacerbations. Up to 40% of patients will have extended periods of time when they are free of disease without treatment. The disease “burns out” in most patients as they become elderly, but not in all. In typical cases of psoriasis, the diagnosis is simple. The appearance of the rash is diagnostic. In atypical cases or with unusual types it is important to rule out other causes of similar appearing eruptions, most importantly fungal infections. It is useful to ask about a family history of psoriasis. It is also useful to examine the nails and buttocks, as findings in these areas can support a diagnosis of psoriasis. Finally, skin biopsy can be useful. However, in cases where the clinical appearance of the disease is atypical, the pathologic findings are usually not diagnostic. Classic pathologic findings include Munro’s microabscesses (accumulations of neutrophils in or directly below the stratum corneum), elongation of the rete ridges, thinning of the suprapapillary plates, and a perivascular lymphocytic infiltrate. Theories on the pathogenesis of psoriasis have changed dramatically over the years. Initially, psoriasis was thought to be primarily an abnormality of keratinocytes. When it was discovered that cyclosporine, a relatively specific immunosuppressant, rapidly and completely cleared psoriasis, the prevailing thought became that psoriasis is primarily an abnormality of the immune system. Clearly, there is genetic predisposition (family history, 65% concordance in monozygotic twins) but also environmental factors (35% of monozygotic twins are discordant). Another interesting observation is that Streptococcal infections often initiate psoriasis or cause flares. This has been attributed to M-proteins on the surface of Streptococci that are similar to keratinocyte proteins, which may lead to misdirected immune responses against keratinocytes. A number of Th1-type cytokines (IL-1, IL-8, IFN-gamma, TNF-alpha, IL-12, IL-23, etc.) have been demonstrated to be upregulated in psoriatic lesions. This has been an active area of research and many of our new effective psoriasis drugs are inhibitors of these pathways. Psoriasis is important to treat because it is a chronic systemic inflammatory disease. Patients with psoriasis have higher cardiovascular mortality compared to patients without psoriasis. Additionally, patients are extremely distressed by the disease. Depression and social avoidance are common. Quality of life studies have shown psoriasis to be equivalent to congestive heart failure in terms of its effect on quality of life of patients. There are generally three types of treatment for psoriasis. They are topical therapy, ultraviolet light therapy, and systemic therapy. Deciding how to treat a given patient depends on severity of disease, risk factors for treatment side effects, and likelihood of compliance. Topical treatments As a general rule, topical treatment can be used for patients with up to 10% of their body involved. It does not work well for disease of the nails, palms, or soles. Topical steroids work well and work quickly, but stop working with prolonged use. Disease is likely to flare when they are discontinued. Potential side effects include thinning of the skin, development of telangiectasia, and systemic absorption if used on a large area of the skin. They should be used only with great caution on the face, around the genitals, axillae, or infra- mammary areas. They should only be used in combination with other topical therapies. Calcipotriene (Dovonex) is a vitamin D analog. It works well, but takes longer to start working than topical steroids. It is very safe. The only significant side effects to be aware of are possible stinging with application and hypercalcemia if used on a very large area for a very long time. Disease does not flare when it is discontinued. Tazarotene (Tazorac) is a vitamin A analog/retinoid. It works very well, but similar to calcipotriene, it works more slowly than topical steroids. Significant side effects include irritation of the skin and birth defects (pregnancy category X). A typical topical treatment regimen would be to apply a mixture of topical steroid and calcipotriene twice daily for a month. After a month, only apply calcipotriene on weekdays and apply the mixture on weekends. This can be done indefinitely if there is any residual disease. Ultraviolet light therapy There are three types of light therapy, ultraviolet B (UVB), narrowband UVB (NBUVB), and psoralen plus ultraviolet A (PUVA). In general, the units for delivering UV light look like upright tanning beds and are located in dermatologist offices. Units for home use are available with a prescription, but are expensive. Ultraviolet B is very safe. It works moderately well, and is especially useful for treating patients with relatively widespread disease. Patients must come to the dermatologist’s office 3 times per week for treatments. Narrowband UVB is much more effective than regular UVB and is also very safe. NBUVB has this name because the wavelengths (wavebands) of light emitted by the lights are very narrow and specific. They are the most effective wavelengths of UVB, isolated and given in high dose. It is also dosed 3 times per week at a dermatologist’s office PUVA is very effective, but it can have significant side effects including severe sunburn-like reactions, and skin cancer with long term use. Patients take a photosensitizing medication one hour before coming to the doctor’s office for their treatment. After taking the medication, they must carefully avoid sunlight for the rest of the day. After a treatment course with PUVA (which make take several months), patients are often free of psoriasis for 6 months to a year. ///Systemic therapy Systemic therapies are used for patients with severe disease involving greater than 10% of their body surface area, or in patients who have psoriatic arthritis. These medications all work very well, but also all have very significant side effects and require careful monitoring by a physician. The most commonly used oral medications are methotrexate, acitretin, and cyclosporine. Methotrexate is used as a once weekly oral dose. It works very well for up to 80% of patients with severe psoriasis. Significant side effects include cirrhosis of the liver (patients must have liver biopsies done when their total dose of methotrexate approaches 1.5-3.0 g) and bone marrow toxicity (regular CBC checks). Patients who drink alcohol, have hepatitis B or C, have diabetes, or are overweight are at increased risk of liver toxicity. Less significant side effects include nausea. Taking folic acid decreases side effects but also decreases effectiveness. Acitretin is a vitamin A derivative. It is given as a once daily dose. The major side-effect is hypertriglyceridemia. This can be controlled with lipid lowering agents, but patients with pre- existing hypertriglyceridemia can be difficult to control. The other significant side effect is birth defects. After a single dose, a woman should not become pregnant for at least three years; therefore it is not given to women who are able to have children. Minor side effects include dry skin, hair loss (regrows when medication stopped), dry lips, dry eyes, and epistaxis. Cyclosporine is an immunosuppressant. It works extremely well, but has very significant side effects. Patients who are on it for over one year are at risk for irreversible loss of renal function. It also increases risk of infections, causes hypertension, and causes electrolyte abnormalities. It is given as a once daily dose. More recently, biologic therapy has revolutionized the treatment of psoriasis. These agents are proteins produced using recombinant DNA techniques. These include monoclonal antibodies to TNF-alpha (infliximab/Remicade, adalimumab/Humira), soluble TNF-alpha receptors (etanercept/Enbrel), and monoclonal antibodies to IL-12/23 (ustekinumab/Stelara). In the short term they have a better risk/benefit ratio than the currently available agents. The long term risks are unknown, although more recent studies have shown that the risk of lymphomas and other cancers from these medications are significantly less than was expected. The biggest problem with these medications is that they are quite expensive (on the order of $15,000 per year). Seborrheic Dermatitis Seborrheic dermatitis is extremely common. The scalp is the most commonly affected area. Other common areas are the eyebrows, nasal creases, cheeks and chest. Men are affected more than women. It tends to be worst in fall/winter and is more common in Caucasians. Seborrheic dermatitis manifests as red plaques or patches with non-adherent, greasy, yellow- white scale. This morphology holds in all the above mentioned areas. In some cases, the scale is fairly minimal (Figure 7.19) (Figure 7.20), and in other cases it is extremely thick and dense (Figure 7.21). Dandruff is generally considered to be a mild form of seborrheic dermatitis on the scalp. Most patients report mild itch. Severe seborrheic dermatitis can be a marker of HIV and some neurologic diseases, especially Parkinson’s. Seborrheic dermatitis is probably caused by inflammatory reactions to species of Malassezia yeast. The yeast lives on the skin of all individuals, and they thrive in oily conditions – hence the distribution of seborrheic dermatitis in oily areas of the skin. Treatment is directed primarily at decreasing yeast populations and secondarily at decreasing inflammation. Ketoconazole cream is first line therapy. Short courses of low potency topical steroids are often combined with chronic ketoconazole therapy. Shampoos containing pyrithione zinc (Head & Shoulders), Selenium Sulfide (OTC or prescription (stronger) Selsun Blue), or ketoconazole 2% work for the scalp, and can also be used to wash the face and chest. Perioral Dermatitis Perioral dermatitis is fairly common in women in their 20s and 30s. It is uncommon in men. Perioral dermatitis presents as erythema, papules, and pustules located around the mouth (Figure 7.22) (Figure 7.23). Patients often report that the skin feels “tight”. A thin (1-2 mm) rim of normal skin separates the lips from the rash. This thin rim of normal skin is one of the most useful findings for differentiating perioral dermatitis from rosacea, and the background redness of the skin is useful for differentiating perioral dermatitis from perioral acne vulgaris. Many, if not most, cases of perioral dermatitis are related to steroid application to the perioral skin. The application may be purposeful, being used initially to treat an unrelated rash, or unintentional, being secondary to “misting” of intranasal steroid spays for rhinitis or steroid inhalers for asthma. The steroids initially cause vasoconstriction, then, in an attempt to restore homeostasis, the body increases resting vasodilatory tone, leading to dilation of the cutaneous vessels, increased cutaneous blood flow, and resultant erythema of the skin. In cases unrelated to steroids, the etiology is unknown. Perioral dermatitis is treated by discontinuing steroid application. This will result in an initial flare of the disease, but it is necessary and unavoidable if a cure is sought. Topical antibiotics with anti-inflammatory effects (clindamycin, metronidazole) are useful, as are oral anti- inflammatory antibiotics, such as doxycycline.