module 6 - dermatological disorders

149
Geriatric Pharmacy Review Module 6: Dermatological Disorders

Upload: geekay79

Post on 19-Dec-2014

142 views

Category:

Documents


1 download

TRANSCRIPT

Page 1: Module 6 - Dermatological Disorders

Geriatric  Pharmacy  Review  

Module  6:  Dermatological  Disorders  

Page 2: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Accreditation Information

ASCP is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

This home study web activity has been assigned 3 credit hours.

ACPE UPN: 0203-0000-10-004-H01-P

Release Date: 3/1/2010

Expiration Date: 3/1/2013

To receive continuing education credit for this course, participants must complete an on-line evaluation form and pass the on-line assessment with a score of 70% or better. If you do not receive a minimum score of 70% or better on the assessment, you are permitted 4 retakes. After passing the assessment, you can print and track your continuing education statements of credit online.

Geriatric Pharmacy Review courses have not yet been approved for Florida consultant pharmacy continuing education.

Page 3: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Content Experts

Current Content Expert:

Kevin W. Chamberlin, PharmD Assistant Clinical Professor of Pharmacy Practice University of Connecticut School of Pharmacy

* with support from Jill K. Logan, 2009 PharmD Candidate, University of Connecticut School of Pharmacy*

Legacy Content Experts:

Nina H. Cheigh, PharmD Clinical Assistant Professor Coordinator, Academic Programs Department of Pharmacy Practice University of Illinois College of Pharmacy

Donna M. Lisi, PharmD, BS, CGP Clinical Pharmacist, Geriatrics New Jersey VA Healthcare System Adjunct Faculty Rutger's University College of Pharmacy

Page 4: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Content Expert Disclosure

Kevin W. Chamberlin, PharmD has no relevant financial relationships to disclose.

Nina H. Cheigh, PharmD, has no relevant financial relationships to disclose.

Donna M. Lisi, PharmD, BS, CGP has no relevant financial relationships to disclose.

Page 5: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Age-related Skin Changes and Pressure Ulcers

Learning Objectives

By the end of this Review Concept you should be able to:

•  Describe common age-related changes of the skin affecting the elderly.

•  Recognize risk factors which predispose older adults to pressure ulcers and complications which may arise.

•  Describe the pathogenesis and clinical features of different stages of pressure ulcers.

•  Use assessment protocols and preventative measures for patients with pressure ulcers.

•  Describe pharmacologic and non-pharmacologic therapies which may be used to treat pressure ulcers and complications associated with pressure ulcer management.

Page 6: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Two Theories of Skin Aging

Two theories of skin aging:

•  Programmatic theory •  Stochastic theory

There are two basic theories related to aging. One programmatic theory states that like development, skin aging is due to an inherent genetic program. The other programmatic theory states that there is random cumulative environmental damage that occurs over ones lifetime to genes and proteins, which ultimately lead to aging. These include ultraviolet radiation, oxidative damage, and heat shock. Currently, it is thought that both theories affect the process of aging.

Page 7: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Clinical Changes in the Aging Skin

Clinical changes in the aging skin:

Epidermis:

Flattened epidermal-dermal junction Keratinocytes - decreased lifespan Melanocytes - decreased number (10-20%) per decade Langerhans cells - decreased number (50%) Decreased vitamin D production

Dermis:

Atrophy - loss of dermal thickness (20%) Fibroblasts - decreased collagen/elastin Blood vessels - decreased number and wall thickness Mast cells - decreased in number Neutral elements - decreased number (30%)

Appendages:

Fat – alteration in thickness Eccrine glands - decreased number and output Apocrine glands - decreased number and output Sebaceous glands - increased size, decreased output Sensory perception – decreased for touch Hair - decreased number of hair follicles and growth rate

Page 8: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Clinical Changes in the Aging Skin

Skin changes that occur with aging lead to gradual decline in the skin’s structure and function. Aged skin typically appears to be drier, wrinkled, less pliant and more prone to trauma. Structural changes are likely responsible for the increased susceptibility to skin disorders. For example, the flattening of the dermal-epidermal junction is responsible for reduced nutrient transfer, and explains the propensity for superficial abrasions following minor trauma. With dermal atrophy, and changes in pigmentation, collagen and elastin, the aged skin is more prone to be wrinkled and dry in appearance.

Other changes in the epidermis include a decrease in cell migration and division, variation in the size, shape and staining properties of the keratinocytes, and a decrease in both melanocytes and Langerhans cells. Similar changes occur in the dermis, which undergoes a corresponding decrease in thickness, vascularity, and elasticity. The loss of vascularity accounts for the pallor, easy bruising, and decreased thermoregulation seen in the elderly. Changes in the dermal layer give the characteristic wrinkled, atrophic appearance of aging skin.

Page 9: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Clinical Changes in the Aging Skin

There is alteration in the thickness of fat, with atrophy occurring in the face and upper and lower extremities, and hypertrophy occurring in truncal areas and the thighs. Adnexal structures such as sweat glands, hair bulb melanocytes and hair follicles become distorted and fewer in number. The decline in specialized nerve endings compromises sensation, making the individual more susceptible to thermal and mechanical injury. Finally, there are prolonged reactions to contact dermatitis due to altered elimination of irritant substances.

Page 10: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Functional Changes That Decline in the Aging Skin

Functional changes that decline in the aging skin:

•  Cell replacement •  Wound healing •  Thermoregulation •  Sweat production •  Sebum production •  Immune responsiveness •  Skin permeability •  Sensory perception

As mentioned in the previous slide, there are many structural changes in skin that occur with aging. Functional problems that result from these structural changes include: altered skin permeability, decreased inflammatory and immunologic responsiveness, impaired wound healing, and decreased thermoregulation. These changes also predispose the elderly to injuries and ulcerations, such as pressure ulcers.

Page 11: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Actinically Damaged (photo-aged) Skin Abnormalities

Actinically damaged (photo-aged) skin abnormalities:

•  Dryness •  Actinic keratoses •  Irregular pigmentation •  Wrinkling •  Coarseness / in-elasticity

Actinic keratoses: trophic reticulated and confluent hypopigmented, red and hyperpigmented crusted eroded plaques. Multiple, symmetric, brown, scaly sand paper-like papules and brown macules.

A prominent feature of actinically damaged, or photoaged skin is elastosis, or skin coarseness. With age, the photodamaged skin displays inflammatory cells such as mast cells and increased fibroblasts. There is increased skin dryness, and a higher propensity for discolorations with sun damage. Wrinkling of photodamaged skin is also exacerbated by cigarette smoking, and possibly by other environmental factors.

Page 12: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Common Cutaneous Disorders in the Elderly

Disorder / Pathophysiology

Neoplasias: UV-induced, cumulative DNA damage which can result in Benign seborrheic keratoses

Seborrheic Keratoses:

•  Multiple 0.5-1.0 cm skin colored to light brown stuck on papules. •  Flat-topped •  Scaly •  Can be extremely pruritic and described as ‘generalized eruptive moles’. •  Eruptive seborrheic keratoses have been associated with internal malignancies.

Squamous cell carcinoma: •  Squamous Cell CarcinomaBasal cell carcinoma •  Malignant melanoma

Page 13: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Common Cutaneous Disorders in the Elderly

Papulosquamous disorder: disturbance of epidermal maturation which can result in:

•  Psoriasis •  Multiple, large, confluent, symmetric red plaques with overlying silver scale •  Dermatitis •  Atopic Dermatitis: symmetric lichenified, excoriated, scaly red confluent plaques.

Pruritus: Result from irritant penetration and cause altered sensation. These can result from:

•  Infections - Result from compromised cutaneous health •  Ulcers - Result from impaired wound healing and structural changes •  Leg Ulcer – Calciphylaxis: symmetric reticulated violaceous erythema, nodules, and punched out ulcers with central black eschars.

Ulceration secondary to stasis dermatitis: diffuse mottled hyperpigmentation, woody edema and multiple punched out ulcers.

•  Bullous pemphigoid - Results from flattening of the dermal-epidermal junction •  Erythematous urticarial papules and large confluent vesicles and bullae

Page 14: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Pressure Ulcers: Incidence, Prevalence and Mortality

Incidence (stage 2 or greater):

•  Overall, 1.5 to 3 million people affected yearly •  Hospitals: 1 – 3% of new admits; 7.7% within 3 weeks •  LTCs: 5% of new admits after 3 months

Prevalence (stage 2 or greater):

•  Hospitals: 28% of patients confined for 1 week or more •  LTCs: 20-33% of patients

Mortality:

•  Accounts for more than 60,000 deaths annually •  Increased for hospital admits and LTC residents •  Most caused by infections secondary to ulcers (e.g., sepsis, cellulitis, osteomyelitis, local infections) •  Worldwide, a lower limb is lost every 30 seconds as a consequence of diabetes

Financial Pressure

•  $15,000 - $27,000 per ulcer •  Estimated costs to healthcare system annually: $5 to $7.5 billion •  Treatment costs are 2.5 times greater than prevention costs

Page 15: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Pressure Ulcers: Incidence, Prevalence and Mortality

Also known as “decubitus ulcers” or “bedsores”, pressure ulcers are a common and serious problem among the elderly. More than fifty percent of all pressure ulcers occur in persons over seventy. The prevalence of pressure ulcers with secondary skin loss is between twenty and thirty percent of patients in nursing homes, and around twenty-eight percent of patients admitted for a week or more in acute care settings. Increased death rates have been observed in elderly patients who develop pressure ulcers, both in the hospital and nursing home. Many of these deaths result from the complications of sepsis and other infections secondary to the ulcer.

Page 16: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Factors in the Pathogenesis of Pressure Ulcers

Skin ulceration occurs with greater pressure and contact time.

Pressure

•  Constant contact pressure between sixty and seventy millimeters of mercury has been known to cause the degeneration of muscle fibers within one to two hours

Shearing forces

Friction

Moisture

A pressure ulcer is a localized area of soft tissue injury resulting from compression between a bony prominence and an external surface. There are four physical factors that contribute to pressure ulcer formation. Constant contact pressure between sixty and seventy millimeters of mercury has been known to cause the degeneration of muscle fibers within one to two hours. Skin ulceration occurs with greater pressure and contact time.

The pressure on bony prominence such as the sacrum can be as high as one hundred to one hundred fifty millimeters of mercury for a patient lying on a hospital bed. Along with tissue degeneration, such pressures can reduce transcutaneous oxygen pressure to zero.

Page 17: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Role of Pressure in the Pathogenesis of Pressure Ulcers

Page 18: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Role of Pressure in the Pathogenesis of Pressure Ulcers

The ischemic effects of pressure appear to trigger the development of pressure ulcers. Injury due to pressure alone begins in the deeper tissues and spreads upward. I f the pressure is relieved, hyperemia may be the only response. I f prolonged, pressure-induced ischemia leads to endothelial swelling and vessel leakage. Eventually hemorrhage occurs, leading to nonblanchable erythema of the skin. The accumulation of edema fluid, inflammatory cells, toxic wastes, and invasive bacteria ultimately suffocate the affected muscle tissue.

Page 19: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Other Factors in the Pathogenesis of Pressure Ulcers

•  Pressure

•  Shearing forces

•  Friction

•  Moisture

Shearing forces, friction, and moisture also contribute to pressure ulcer formation. Shearing forces occur when two tangential surfaces slide on each other, as when a supine patient slides to the foot of the bed. Shearing forces can lower the amount of pressure necessary to occlude blood vessels and cause damage to the epidermis. Friction, which occurs any time a patient is pulled across a sheet and can cause a loss of epithelial cells.

Moderate amounts of moisture increase the amount of friction at the rubbing interface, and lead to maceration and epidermal injury.

Page 20: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Risk Factors for Pressure Ulcers

•  Unrelieved pressure

•  Immobilizing or activity-limiting disease processes, including physical

restraints

•  Repeated exposure to pressure

•  Incontinence

•  Nutritional factors (e.g., malnutrition, hypoalbuminemia)

•  Altered level of consciousness, including sedating medications

•  Dry skin (xerosis)

•  Increased body temperature / fever

• Decreased blood pressure

• Anemia

• Circulation deficiencies

• Diabetes mellitus

• Diaphoresis

• Edema

• Overweight or underweight

• Pruritus

• Hypotension

• Restless legs syndrome

Page 21: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Risk Factors for Pressure Ulcers

Normal capillary filling pressure is thirty-two millimeters of mercury. Increased unrelieved pressure for a short time or low uninterrupted pressure for a long time can result in pressure ulcers. Age-related changes to the skin and increased susceptibility to disease are important risk factors for the elderly. Any disease or healing process that leads to prolonged immobility increases the risk of pressure ulcers.

Other risk factors include fecal incontinence, dry skin, and altered level of consciousness. Nutritional factors that are significantly related to pressure ulcer development include decreased lymphocyte count, hypoalbuminemia, inadequate dietary intake, and decreased body weight. Common pressure ulcer points include the sacrum, greater trochanter, ischium, medial and lateral condyles, malleolus, and heels.

Page 22: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

AHRQ Guidelines for the Prevention and Treatment of Pressure Ulcers

AHRQ Guidelines for the Prevention and Treatment of Pressure Ulcers

•  Relieve pressure to bony prominences

•  Assess bed- and chair-bound patients for additional risk factors

•  Systematically inspect skin daily

•  Clean skin with mild cleansing agent as needed and on a routine basis; avoid hot water

•  Use lubricants to relieve pressure injuries

•  Minimize skin drying with climate control and moisturizers

•  Minimize skin exposure to moisture from incontinence, perspiration, or wound drainage

•  Minimize skin injury due to friction and shear through proper positioning, transferring, and turning techniques, and the

use of lubricants and protective films

•  Avoid massage over high risk skin areas

•  Ensure adequate dietary intake and correct nutritional deficiencies

•  Institute rehabilitation efforts where feasible

•  Use wound care products appropriately

•  Minimize pressure ulcer colonization

•  Identify early signs of infection and treat promptly

•  Provide adequate pain management

•  Conduct psychosocial assessment to assess compliance with regimen, if possible

Page 23: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

AHRQ Guidelines for the Prevention and Treatment of Pressure Ulcers

To prevent the discomfort and infectious complications associated with pressure ulcers, prevention and treatment interventions must be prompt and thorough. The Agency for Healthcare Research and Quality has developed a set of guidelines for skin care and early treatment of pressure ulcers.

Page 24: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Assessment of Patients with Pressure Ulcers

Pressure Ulcer Work-up:

•  Thorough patient history •  Pain evaluation •  Nutritional evaluation •  Identification of risk factors •  Physical exam & Ulcer inspection

Pressure Ulcer Assessment: •  Location •  Appearance

•  Color or depth •  RED: partial thickness loss; moist; painful; minimal necrotic tissue •  YELLOW: tissue loss through the dermis; devitalized/necrotic tissue is grey/yellow (slough) •  BLACK: eschar (thick, leathery, necrotic tissue)

•  Size •  Length, width, depth

•  Stage •  Status •  Eschar formation

–  A thick, coagulated crust or slough which develops following a thermal burn or chemical or physical cauterization of the skin

http://www.rnao.org/bestpractices/PDF/BPG_Pressure_Ulcer.pdf

Page 25: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Assessment of Patients with Pressure Ulcers

The appropriate management of patients with pressure ulcers depends on the assessment and treatment of any underlying conditions that may increase the risk of ulceration and/or prevent the lesions from healing. This includes a nutritional assessment and carefully recording the size, stage, and location of each ulcer. The condition of the skin at the site of the ulcer is critical.

Surrounding erythema may represent cellulitis, while purulent drainage suggests local wound infection. The presence of a darkly pigmented eschar or necrotic tissue calls for surgical debridement. Bacteriologic studies are indicated in patients presenting with sepsis, osteomyelitis, or cellulitis.

Assess all patients for pain related to pressure ulcers or their treatment. All individuals being treated for pressure ulcers should undergo a psychosocial assessment to determine their ability and motivation to comprehend and adhere to treatment, if possible.

Page 26: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Prevention of Pressure Ulcers

Prevention of Pressure Ulcers

•  Identify patients at risk

•  Eliminate risk factors, if possible

•  Proper positioning and repositioning every 1-2 hours

•  Pressure-reducing devices (e.g., mattresses, cushions, pads, pillows)

•  Lifting devices (to minimize friction and shear)

•  Education of caregivers and patients

•  Use of skin moisturizers if skin is dry

Page 27: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Prevention of Pressure Ulcers

Preventative measures include reducing or eliminating factors contributing to the development of ulcers, such as prolonged uninterrupted pressure, friction, shearing force, malnutrition and incontinence. Proper positioning and frequent repositioning is key to reducing the risk of pressure ulcers.

Unfortunately, the regular application of these techniques is not always sufficient or possible. Patients who cannot tolerate frequent turning, who are immobile, who have very large or multiple ulcers or who have ulcers that have not responded to treatment may need the use of pressure support surfaces.

The use of thick foam, air, or water mattresses, air fluidized or low air loss beds, sheepskin or foam pads, and other pressure-reducing devices may help some patients at high risk for pressure ulcers. Caregiver and patient education can also play a significant role.

Page 28: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Stages of Pressure Ulcers

STAGE I

•  Nonblanchable erythema of intact skin

•  In individuals with darker skin, skin will discolor

•  Warmth, erythema, induration, or hardness may also be indicators

http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=-962687846

http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=167341289

Page 29: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Stages of Pressure Ulcers

STAGE II

• Partial-thickness skin loss involving epidermis, dermis, or both

• Ulcer is superficial and presents clinically as an abrasion, blister, or shallow center

http://hab.hrsa.gov/tools/palliative/chap25.html

STAGE III

• Full-thickness skin loss • Involves damage or necrosis of subcutaneous tissue,

possibly extending to underlying fascia • Presents as deep crater +/- undermining of adjacent

tissue

http://hab.hrsa.gov/tools/palliative/chap25.html

Page 30: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Stages of Pressure Ulcers

STAGE IV

•  Full-thickness loss

•  Extensive destruction, tissue necrosis, or damage to muscle, bone, or supporting structure(s)

•  Undermining and sinus tracts may also occur

http://hab.hrsa.gov/tools/palliative/chap25.html

http://hab.hrsa.gov/tools/palliative/chap25.html

Page 31: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Stages of Pressure Ulcers

Staging of pressure ulcers is important in formulating a treatment plan.

Stage I includes pressure ulcers with an observable pressure-related alteration of intact skin whose indicators as compared to an adjacent or opposite area on the body may include changes in one or more of the following: skin temperature (warmth or coolness), tissue consistency (firm or boggy feel), and/or sensation (pain, itching). The ulcer appears as a defined area of persistent redness in lightly pigmented skin, whereas in darker skin tones, the ulcer may appear with persistent red, blue, or purple hues.

Stage II includes pressure ulcers with partial thickness skin loss involving epidermis, dermis, or both. The ulcer is superficial and presents clinically as an abrasion, blister, or shallow crater.

Stage III includes pressure ulcers with full thickness skin loss involving damage to, or necrosis of, subcutaneous tissue that may extend down to, but not through, underlying fascia. The ulcer presents clinically as a deep crater with or without undermining of adjacent tissue. Think of it as an ulcer that is about as deep as a nickel or house key is thick.

Stage IV includes pressure ulcers with full thickness skin loss with extensive destruction, tissue necrosis, or damage to muscle, bone, or supporting structures (e.g., tendon, joint, capsule). Undermining and sinus tracts also may be associated with Stage IV pressure ulcers.

Page 32: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Status of a Wound

Phase 0: Initial injury

Phase I: Inflammation •  Characterized by edema, erythema, heat, and pain •  Lasts 4 – 6 days •  Neutrophils, monocytes, and macrophages migrate

to the wound

Phase II: Proliferation •  Begins within hours of the injury •  Lasts 4 – 24 days •  New granulation tissue is formed

Wound Healing Phases

Phase III: Maturation • Remodeling occurs • Lasts 21 days to 2 years • Red granulation tissue is transformed into white

vascularized tissue and a scar is formed

• Wound factors that can delay: • Continued pressure • Dry wound environment • Wound edema • Repetitive trauma • Local infection • Tissue necrosis

• Patient factors that can delay: • Advanced age • Malnutrition • Decreased vascular perfusion • Immunosuppression

Page 33: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Status of a Wound

Wounds heal by progressing through three stages after the initial injury: inflammation, proliferation, and maturation. During the inflammatory phase, neutrophils and macrophages destroy the bacteria and clean the wound of debris. Monocytes and macrophages produce cytokines, such as interleukin-1 and others, to promote the growth of new tissue.

Next, growth factors stimulate proliferation and migration of fibroblasts to the wound area and promote angiogenesis, or the formation of new blood vessels. The newly granulated tissue that is formed consists of macrophages, fibroblasts, and immature collagen.

The final phase of wound healing is maturation. This can take weeks to years to complete, and is complicated by numerous wound and patient-related factors listed on your screen.

Page 34: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Pharmacological Interventions

Monotherapy:

•  Ampicillin/sulbactam 1.5-3 gm (total) IV or IM q 6 h •  Imipenem 0.25-1 gm IV q 6-8 h or 500-750 mg IM q12 h •  Ticarcillin/clavulanate 200-300mg/kg/day given IV q4-5 h •  Piperacillin/tazobactam 3.375 mg IV q 6 h •  Clindamycin 600-1200 mg IM/IV q 6-12 h or 150-450 mg p.o. q 6 h •  Metronidazole 7.5 mg/kg p.o. or IV q 6 h (maximum 4 gm)

Polytherapy:

•  Clindamycin or metronidazole + aminoglycoside (e.g., gentamicin 3-5 mg/kg IV/IM in divided doses) or fluoroquinolone

Systemic interventions are central to managing patients with pressure ulcers. Empiric antibiotic treatment should cover both aerobic and anaerobic organisms, as these wounds are typically polymicrobial. Organisms most frequently isolated from pressure ulcers include: Staphylococcal species, Streptococcal species, Enterobacteriaceae, Pseudomonas aeruginosa, and anaerobes.

Empiric antibiotic regimens may include monotherapy with a beta-lactam antibiotic targeting the popular gram positive organisms, or with various broad-spectrum combinations listed on your screen. A number of new antibiotics targeting skin and soft-tissue indications are in development or under review by the FDA. Additionally, many antibiotics need doses adjusted for renal and / or liver dysfunction, so beware. Refer to the infectious diseases module for more information.

Page 35: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Nutritional Interventions

Protein •  1 - 1.5 gm/kg of body weight

Vitamin C •  500 mg orally twice to three times a day

Multivitamins

Zinc supplements, if zinc-deficient •  220 mg of zinc sulfate orally twice to three times a day

Adequate fluids

Healthy diet

Page 36: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Nutritional Interventions

With respect to nutritional factors, studies have shown that protein ingestion can improve the healing of pressure ulcers. A diet composed of twenty-five to thirty kilocalories per kilogram of body weight is adequate for most patients. Targeting albumin concentrations in the therapeutic range will greatly decrease the likelihood of ulcer formation, or greatly assist in ulcer healing.

The authors provide a table that associates hypoalbuminemia with ulcer stages that they are likely to develop at those low levels of nutritional status. The use of Vitamin C, zinc, and multivitamins have all been considered, with controversial evidence of its efficacy.

Zinc may improve healing in zinc deficient patients, but zinc levels should be checked prior to initiation since high zinc levels may impair wound healing. Additionally, maintaining adequate fluid intake and minimizing sugars in the diet will aid in promoting a healthy wound healing environment.

Page 37: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Wound Care Cleansing

These can disturb granulation tissue:

•  Povidone Iodine (Betadine®) •  Chlorhexidine gluconate (Hibiclens®) •  Sodium hypochlorite solution (Dakin’s®) •  Hydrogen peroxide 3% (standard OTC strength)

•  20% might enhance healing •  Acetic acid solution

USE: Normal saline

Cleansing should be done as a routine part of the initial assessment, and then periodically with dressing changes. The purpose of cleaning is to remove devitalized tissue and to decrease the bacterial burden to the wound area. Normal saline is the preferred cleansing agent; it is physiologic, will not harm tissue, and effectively cleans most wounds. The other agents listed on your screen are generally considered cytotoxic to the wound granulation tissue and should be avoided.

Page 38: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Wound Care Products

Pressure ulcers require dressings to maintain their physiologic integrity.

The use of dressings and other wound care products depends on the stage of pressure ulcer and its characteristics.

Film dressings appropriate for Stage One and Stage Two ulcers include Biocculsive®, Tegaderm®and Op-Site®These dressings are permeable to gases and vapors but not to fluid. They usually need to be changed every five to seven days. Hydrocolloid dressings are useful for smaller, solitary Stage Two or Stage Three pressure ulcers and include: Duoderm®, Comfeel®Restore®These dressings contain an adhesive material that physically interacts with wound fluid to form a moist gel that promotes cell migration, cleansing, debridement and granulation.

Unless exudative leakage occurs, hydrocolloid dressings are changed every seven days. Hydrogel dressings include Vigilon® and GelSyte®. These hydrophilic polymers are useful in dry wounds where minimal exudate is present. Dressings may be left on for one to three days. Calcium alginate dressings include Sorbasan® and Kaltostat®. These dressings are derived from seaweed and are highly absorbent. If the wound has heavy exudate, the dressing should be changed once or twice daily. As the ulcer heals, the dressing may be left on for several days.

Page 39: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Debridement of Pressure Ulcers

Sharp / surgical Scalpel, scissors

Mechanical Hydrotherapy, wet-to-dry dressings, etc.

Enzymatic / chemical Collagenase, chlorophyll, papain, collagenase

Autolytic Synthetic dressings (hydrocolloid, hydrogel)

Debridement may be augmented with absorptive dressings (e.g., Debrisan®, HydraGran®

Page 40: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Debridement of Pressure Ulcers

Debridement is the process of removing non-living tissue.

Debridement of pressure ulcers is indicated when necrotic tissue is present. The purpose is to aid in the healing process, and reduce bacterial infection.

There are four methods of debridement that are employed, with no single method preferred over the other:

Enzymatic debridement involves the use of a topical agent such as chlorophyll, papain, or collagenase to dissolve the necrotic tissue. Autolytic debridement involves the use of the enzymes present in the wound to aid in dissolving the devitalized tissue. Autolytic debridement is accomplished by utilizing moist wound dressings such as a hydrocolloid or a hydrogel. Mechanical debridement involves allowing moist gauze to dry and adhere to the tissue prior to removal. This is often painful for the patient and can remove viable and nonviable tissue. Sharp debridement is a surgical procedure utilizing a scalpel or scissors to remove dead tissue. This can be performed at the bedside or in the operating room depending on the extent of debridement needed. After surgical debridement, the wound will be packed with a dry dressing for a day to control bleeding.

Afterwards, moist dressings are applied to promote wound healing. Moist dressings are also used after mechanical, chemical, and autolytic debridement. Many factors contribute to wound healing, which frequently can take considerable time. Debridement may need to be repeated.

Page 41: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Specialized Beds and Local Wound Care

Specialized Devices: •  Air-fluidized or low air loss bed

Local Wound Care: •  Topical antibiotics - gentamicin, silver sulfadiazine, triple antibiotics, normal saline •  Topical anesthetics are contraindicated (use systemic analgesics) •  Skin cleanser or antiseptic agents should be avoided •  Topical Phenytoin

RS Rhodes, CA Heyneman, VL Culbertson, SE Wilson, and HM Pataki. Topical phenytoin treatment of stage II ulcers in the elderly. The Annals of Pharmacotherapy: Vol. 35, No. 6, pp. 675-681.

The treatment of pressure ulcers includes all of the interventions described for the prevention: proper positioning, frequent repositioning, and pressure-reducing devices.

Topical antibiotics may have a limited role as they have been shown to lower bacterial counts. But they must be used cautiously as some products may cause hypersensitivity reactions.

If there are signs of systemic infection, topical antibiotic therapy is insufficient. Topical antiseptics such as hypochlorite solution, providence-iodine, acetic acid and hydrogen peroxide should be avoided because they inhibit wound healing. Topical anesthetics and skin cleansers should also be avoided.

Pain should be managed using non-topical routes of administration. Additionally, topical phenytoin has also been shown to be helpful in wound healing through its actions in stimulating epithelial growth similar to the known side-effect of gingival hyperplasia. Currently its place in therapy is not defined and further research is necessary before recommending this modality.

Page 42: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Drug Therapy and Wounds

Drugs Associated with Decreased Wound Healing •  Corticosteroids •  Methotrexate •  Tetracyclines

Drugs Associated with an Increased Risk of Wound Development •  Antipsychotics •  Opioids •  Anxiolytics •  Antidepressants

Specialty Drugs for Additional Treatment Options •  Becaplermin (Regranex®)

•  Platelet-derived human growth factor •  Topical gel (0.01%) •  Enhances formation of new granulation tissue and induces fibroblast proliferation to promote wound healing

A number of drugs have been associated with either decreasing the state of the environment for the wound to heal in, or increasing the risk of wound development. For many, the reasons of association can be inferred: perhaps via increasing sedation or decreasing sensation. Some, like tetracycline’s, have been shown to thin the skin over chronic usage, thus increasing the risk of a wound developing. Chronic or high-dose glucocorticoid use is associated with reduced collagen synthesis through inhibiting the inflammatory component of skin growth. Steroids also inhibit epithelialization wounded tissue.

Page 43: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Advanced Wound Care

Wound VACs

•  Vacuum-assisted closure •  FDA approved for promotion of wound healing for patients with:

•  Diabetic foot wounds •  Pressure ulcers •  Chronic wounds •  Acute and traumatic wounds •  Dehisced surgical wounds •  Partial-thickness burns •  Flaps and grafts

•  Good for large stage III and IV wounds •  Not good for:

•  Necrotic tissue •  Exposed vessels •  Active bleeding •  Those on anticoagulant therapy

VAC therapy is a sub-atmospheric pressure technique (vacuum-assisted closure) which entails placing an open-cell foam dressing into the wound cavity and applying a controlled subatmospheric pressure of 125 millimeters of mercury below ambient pressure.

VAC therapy employs this negative pressure through a closed system, removing fluid from open wounds through a sealed dressing and tubing which is connected to a collection container.

Page 44: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Advanced Wound Care

VAC therapy is extremely useful in dealing with chronic wounds that do not respond to conventional treatments. Although VAC initially appears an expensive option, when the speed of healing is taken into consideration, then the treatment is cost-effective and must be considered. VAC therapy has been proven to be cost-efficient, safe, and effective as a treatment modality in wound care even in those patients with impaired physiologic reserve and/or highly contaminated.

Page 45: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Complications of Pressure Ulcers

Complications of Pressure Ulcers

•  Osteomyelitis •  Bacteremia •  Advancing cellulitis •  Amyloidosis •  Endocarditis •  Heterotopic bone formation •  Maggot infestation •  Meningitis •  Perineal and urethral fistula •  Septic arthritis •  Sinus tract involvement or abscess •  Squamous cell carcinoma

When you consider that the skin is your body’s first line of defense against infections, it should be no surprise that if compromised by an ulcer the complications can be far ranging. For example, if left untreated, pressure ulcers can lead to osteomyelitis, bacteremia and advancing cellulitis. Ultimately, patients with pressure ulcers have a higher morbidity and mortality.

Page 46: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Resources

For additional information, see:

Bakker K, Abbas ZG, Pendsey S. Practical Diabetes International. 2006;23(8):365-369.

Bates-Jensen BM, et al. The minimum data set pressure ulcer indicator: does it reflect differences in care processes related to pressure ulcer prevention and treatment in nursing homes? J Amer Geriatric Soc. 2003;51:1203-1212.

Bermann PE. Aging skin: causes, treatments, and prevention. Nurs Clin N Am. 2007;42:485-500.

Cannon BC, Cannon JP. Management of pressure ulcers. AJHP. 2004;61:1895-1907.

Clinical Practice Guideline No. 3: Pressure Ulcer in Adults: Prediction and Prevention. Rockville, MD: Agency for Health Care Policy and Research, U.S. Dept. of Health and Human Services, May 1992.

Dao H Jr, Kazin RA. Gender differences in skin: a review of the literature. Gend Med. 2007;4:308-328.

Dinh T, Pham H, Veves A. Emerging treatments in diabetic wound care. Wounds. 2002;14(1):2-10.

Evans JM, Andrews KL, Chutka DS, Fleming KC, Garness SL. Pressure ulcers: prevention and management. Mayo Clin Proc. 1995;70:789-799.

Page 47: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Resources

Federman D, Hogan D, Taylor R, Caralis P, Kirsner RS. A comparison of diagnosis, evaluation and treatment of patients with dermatological disorders. J Am Acad Dermatol. 1995;32:726-729.

Landi F, et al. Topical treatment of pressure ulcers with nerve growth factor. Ann Int Med. 2003;139:635-641.

Pinchcofsky-Devin GD, Kaminski MV Jr. Correlation of pressure sores and nutritional status. J Am Geriatric Soc. 1986;34(6):435-440.

Reddy M. Skin and wound care: important considerations in the older adult. Adv Skin Wound Care. 2008;21:424-436.

Rhodes RS, et al. Topical phenytoin treatment of stage II ulcers in the elderly. Ann Pharmacother. 2001;35(6):675-681.

Rook JL. Wound care pain management. Adv Wound Care. 1996;9(6):24-31.

Smith DM. Pressure ulcers in the nursing home. Ann Intern Med. 1995;123:433-442.

Websites: http://www.rnao.org/bestpractices/PDF/BPG_Pressure_Ulcer.pdf

www.dermatlas.org

Page 48: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Inflammatory Skin Disorders that Affect the Elderly

Learning Objectives

By the end of this Review Concept you should be able to:

• Describe the etiology, clinical presentation and pharmacological treatment of common inflammatory disorders including xerosis, pruritis, statis dermatitis, contact dermatitis, seborrheic dermatitis, psoriasis, fungal infections of the skin, rosacea and allergic reactions of the skin.

• Construct a therapeutic regimen for an individual presenting with an inflammatory skin disorder, including both non-pharmacologic and pharmacologic modalities.

Page 49: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Clinical Presentation of Xerosis

Etiology: •  Linked to abnormalities in the keratinocyte maturation process

Clinical Presentation: •  Dry Scaly Skin •  Delineation of corneocytes •  Pruritis

A 75 year old man complained of burning and itching of his legs. The rash typical of eczema craquelé settled down quickly with lubricants and a short course of topical steroids.

One of the most common dermatological disorders among the elderly is xerosis, or “dry skin.” Although the exact etiology is unknown, the onset of xerosis may be linked to minor abnormalities in the keratinocyte maturation process. Frequent bathing without the subsequent application of emollients is often cited as a contributing factor.

The clinical presentation of xerosis is marked by dry scaling skin with delineation of the corneocytes, especially on the lower extremities. Itching is common and pruritus is often prominent. The condition is often exacerbated in the winter months due to the lower humidity and increased time spent in heated rooms. If untreated the involved skin may become inflamed, a condition known as erythema craquelé or asteatotic eczema.

Page 50: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Management of Xerosis

Baths •  Tepid water •  Every other day

Topical emollients •  With lanolin, glycerin, or petrolatum

Urea 10-20%

Lactic acid 5% or 12%

Avoid strong soaps, rubbing alcohol, detergents and other drying agents

Avoid irritants to skin e.g., wool

Avoid scented moisturizers

Keep air in home humid

The discomfort of xerosis may be relieved by a few simple changes.

For example, taking less baths; potentially every other day with tepid water is helpful. Application of a topical emollient should be within 3-5 minutes after coming out of the bath.

Ingredients such as lanolin, glycerin, and petrolatum help to occlude the skin and retain moisture.

Ingredients such as urea or lactic acid products help to increase moisture by sloughing off dead skin cells.

Caution should be used with these products as they can result in some stinging and burning and definitely should not be applied to open wounds.

The avoidance of detergents, strong soaps, and scented products can also help reduce irritation.

Moreover, maintenance of approximately 60% humidity in the air allows for skin to maintain its normal moisture.

Page 51: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Pruritus: Common Causes

Skin Disorders: •  Eczema •  Scabies •  Xerosis

Systemic Disease: •  Chronic renal or liver failure •  Thyroid disease •  Iron deficiency •  Malignancy •  Hematologic disorders •  Diabetes Mellitus

Drug Ingestion: •  Opioids •  Drugs which cause cholestasis •  Aspirin •  Quinidine •  Psoralen •  Parabens

Pruritus is defined as the sensation that causes the desire to scratch.

Senile pruritus is pruritus of unknown origin in the elderly. Pruritus may represent common symptoms of dermatological conditions such as eczema, scabies or xerosis.

It may represent signs of systemic disease such as chronic renal or liver failure, thyroid disease, iron deficiency, malignancy, or hematologic disorders. It may also be the result of ingesting opioids, aspirin, quinidine, psoralen, parabens and drugs that cause cholestasis.

Sudden onset pruritus is more likely to be caused by systemic problems such as chronic renal failure or drug-induced cholestasis. Additionally, irritants causing contact dermatitis such as detergents should be considered.

Page 52: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Diagnosis of Pruritus

•  Rule out any skin disease •  Inquire about contact with irritants or allergies •  Laboratory workup to rule out systemic disease

•  Complete Blood Count with differential •  Free T3 and T4 •  Liver Function Tests •  Electrolytes with Blood Urea Nitrogen and Creatinine •  Chest X-ray

Most patients with pruritus present with excoriations or other evidence of scratching. Many may have a primary subcutaneous eruption as well.

In the absence of primary skin lesions, a thorough history and physical exam are essential to uncovering any underlying systemic diseases. Laboratory tests can be used to rule out systemic disease.

In cases where the history and physical exam are inconclusive, a more thorough laboratory work up using the tests listed on your screen may help identify the underlying cause.

Page 53: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Pruritus

•  Treat underlying cause, if known •  Lubricants or moisturizing agents •  Topical anesthetic •  Antihistamines •  Topical corticosteroids

If known, treatment is directed at the underlying disease. Symptomatic treatments include emollients such as Sarna®, which contains menthol and phenol. Such emollients are most effective when applied after a shower or bath.

Topical anesthetics may provide temporary relief, but expose the patient to allergic sensitization. If the skin is dry, lubricants or moisturizing agents may provide relief.

Oral antihistamines have limited effectiveness and produce many untoward side effects in the elderly. Topical corticosteroids are usually contraindicated for patients with normal-looking skin.

Page 54: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Types of Dermatitis

Types of Dermatitis

•  Stasis dermatitis •  Contact dermatitis •  Seborrheic dermatitis

Another inflammatory skin disorder that commonly afflicts the elderly is dermatitis. Dermatitis refers to a superficial inflammation of the skin due to irritant exposure, allergic sensitization, genetic causes, or idiopathic factors.

There are at least three types of dermatitis each with its own distinctive etiology and clinical features. Stasis dermatitis is caused by chronic venous insufficiency leading to increased hydrostatic pressure and transudation of fluid and red cells. Contact dermatitis can be caused by an allergic reaction or by non-immunological chemical irritation.

The etiology of seborrheic dermatitis is unknown.

Page 55: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Stasis Dermatitis

Etiology: Secondary to decreased peripheral circulation

Clinical Presentation: Peripheral edema Red-brown discoloration of legs Inflammation Pruritis Ulceration

Venous Stasis

Venous Stasis Ulcer

Stasis dermatitis is often secondary to decreased peripheral circulation. This results in increased peripheral edema and a red-brown discoloration of the lower legs, the color being caused by the accumulation of hemosiderin deposits. Inflammation and pruritus are common. Minor trauma to the area may cause ulceration.

Page 56: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Stasis Dermatitis and Venous Stasis Ulcers

Stasis Dermatitis:

•  Elevation of legs and reduction of edema •  Correction of venous insufficiency (if possible) •  Low potency topical corticosteroids (e.g., 1% Hydrocortisone ointment) for inflammation and pruritus •  Use of support hose •  Avoidance of contact allergens

Venous Stasis Ulcers:

•  Local wound care epidermal allografting •  Hydrocolloid dressings (e.g., Duoderm®)

Ulcerated dermatitic patches and plaques

Chronic Venous Stasis

Page 57: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Contact Dermatitis

Acute - erythematous, pruritic, vesicular eruptions

Subacute - dry scales and papules

Chronic - slightly scaly

Contact dermatitis is defined as an altered state of skin reaction induced by exposure to an allergen or irritant. It may be acute, subacute, or chronic. Acute contact dermatitis is characterized by eruptions that are erythematous, pruritic, and vesicular. The chronic variety, in contrast, tends to be only slightly scaly. During the subacute phase, the skin may have dry scales and papules.

Page 58: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Etiology of Contact Dermatitis

Allergic – onset may be hours or days after exposure to an allergen

Irritant – onset may occur upon first or repeated exposures to the irritant; involves the hands, face, neck, axilla, and trunk of the body

Because the clinical manifestations of allergic and irritant contact dermatitis are virtually identical, the etiology of the disorder plays a crucial role in diagnosis and treatment. Allergic contact dermatitis may show up hours to days after exposure to an allergen. Irritant contact dermatitis can occur upon first or repeated exposures to the irritant, and usually involves the hands, face, neck, axilla, and trunk of the body. Irritant contact dermatitis may also be caused by local anesthetics or neomycin.

Page 59: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Management of Contact Dermatitis

Primary Goals: •  Identification and removal of offending agent •  Relief of symptoms

Symptomatic Treatment: •  Soap-free cleansers, colloidal oatmeal •  Astringents

•  Aluminum acetate •  Burrow’s solution •  Witch hazel

•  Lubricants •  Oral antihistamines

Initial treatment of contact dermatitis should always focus on identification and removal of the offending agent. When this is not possible, the patient should be advised to avoid exposure to those agents considered most likely responsible. An immediate goal of treatment is the relief of symptoms.

Products that relieve itching, rehydrate the skin, and decrease weeping of the lesions will provide some immediate relief. The dosage form of topical preparations is determined by the stage of inflammation. In the acute stage, wet dressings are preferred because ointments and creams further irritate the tissue.

Astringents such as aluminum acetate, Burrow's solution or witch hazel decrease weeping from lesions, “dry out” the skin, and provide relief from itching. These agents are applied as wet dressings and should not be used for more than seven days.

For chronic dermatitis, lubricants, emollients, or moisturizers should be applied after bathing. Soap-free (or mild) cleansers, and products containing colloidal oatmeal, also contribute to alleviating itch and soothing the skin.

Page 60: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Pharmacologic Treatment of Contact Dermatitis

Topical Corticosteroids:

•  Amcinonide cream, lotion & ointment 0.1% •  Betamethasone dipropionate cream & ointment 0.05% •  Betamethasone valerate ointment 0.1% •  Clobetasol propionate cream, ointment, gel, solution, and spray 0.05% •  Desoximetasone cream &ointment 0.25%, gel 0.05% •  Diflorasone diacetate ointment 0.05% •  Fluocinolone acetonide cream 0.01%, 0.025% •  Fluocinonide cream, ointment & gel 0.05% •  Halcinonide cream & ointment 0.1% •  Halobetasol propionate cream & ointment 0.05% •  Triamcinolone acetonide ointment 0.025%, 0.05%, 0.1%, 0.5%

Other Medications:

•  Antihistamines •  Antibiotics (oral, parenteral)

Page 61: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Pharmacologic Treatment of Contact Dermatitis

Contact dermatitis usually responds to treatment by potent topical corticosteroids chosen for the specific body site involved. More severe cases may be treated with oral prednisone.

However, corticosteroids should not be used if infection is present and should not be applied over large areas. Furthermore, as a general rule of thumb, the higher the potency of the steroid the more likely it is to cause local tissue atrophy, degeneration and striae.

Therefore, very high potency products should be used for very short periods of time on the face and intertriginous areas if at all. American Academy of Dermatology guidelines recommend the use of both topical and systemic treatment.

Antihistamines may be taken systematically or applied topically. Antibiotics should be used only if signs of infection are present.

Page 62: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Seborrheic Dermatitis

Seborrheic Dermatitis •  Etiology: unknown, may be abnormality of skin lipids, and increased Pityrosporum ovale (yeast) •  Affects 3-5% of the population

Signs and Symptoms: •  Lesions with oily scales and crusts •  Mild erythema and inflammation •  Typically around the nose, cheeks, scalp, and upper part of trunk

Example 1

Goals:

• Loosen and remove scales • Inhibit yeast colonization • Control secondary infection • Control itching and erythema

Therapy:

• 1-2.5% selenium sulfide • Salicylic acid • Coal tar • Zinc pyrithione • 2% ketoconazole • Topical steroids • Tacrolimus ointment • Pimecrolimus cream

Page 63: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Seborrheic Dermatitis

Seborrheic dermatitis is a common chronic disease with unknown etiology. It affects at least 3-5% of the U.S. population, and peaks in infancy, and later around the fourth to seventh decades of life. Seborrheic dermatitis is associated with oily-looking skin, although increased sebum production is not always detected. There seems to be a mild abnormality of the skin lipids, and a higher count of Pityrosporum ovale, a lipophilic yeast that is commonly found on the skin.

Skin lesions of seborrheic dermatitis are typically characterized by a yellowish color, mild to moderate erythema and inflammation. There tends to be an oily appearance, with scales and crusts. In adults, it is commonly found on the face, typically around the nose and cheek regions. Seborrhea can also be found on the scalp, upper part of trunk, and other areas that have increased sebaceous follicles.

Overall, seborrheic dermatitis has 4 major goals of therapy: To loosen and remove the scales, prevent yeast colonization, control any secondary infections, and reduce itching and erythema. Interestingly, the disease typically seems to improve with warmer weather and worsens with colder air. There are many topical agents used to manage seborrheic dermatitis.

Depending on what area of the body is affected, the pharmacist can assist in selection of proper vehicles such as solutions or shampoos for scalp. Ingredients such as selenium sulfide, salicylic acid, and coal tar can help soften and remove the scales. Seborrheic dermatitis responds very quickly to low potency topical corticosteroid preparations but judicious use is important to avoid long term effects. Topical ketoconazole 2% can also be used to help control the yeast colonization.

Page 64: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Psoriasis

Psoriasis •  Affects 2% of the population with peaks at ages 20 and 55 years •  Genetically influenced with defects in the epidermal cell cycle

Signs and Symptoms: •  Sharply demarcated erythematous papules and plaques; silver-white •  Can appear on torso, arms, legs, soles, palms, genitalia, face, and nails •  Psoriatic arthritis can also occur

Example 1

Trigger factors:

•  Physical trauma (The Koebner phenomenon) •  Infections •  Stress •  Drugs (beta blockers, lithium)

Page 65: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Psoriasis

Psoriasis is a chronic, genetically influenced, immunologic disease that results in remitting and relapsing scaly and inflamed plaques. Evidence suggests a defect in the epidermal cycle in that psoriatic skin tends to replicate at a rate sevenfold faster than that of normal skin. It affects two percent of the general population and there is a peak of onset first around the age of 20, then a second around the age of 55.

The clinical appearance of psoriasis, although not scarring, can be cosmetically disfiguring. Psoriatic lesions are usually very sharply demarcated with erythematous papules and plaques, generally with a silver-white scale.

If the scale is removed, there is a pink lesions that lies exposed and perhaps with punctuate bleeding called the Auspitz sign. Psoriasis can be present anywhere, including the scalp, trunk, arm, legs, palms, soles, face, and genitalia. Often nail beds are affected with yellowish spots. At times, distal fingers can develop an inflammatory arthritis which is collectively referred to as psoriatic arthritis.

External factors can trigger psoriatic skin lesions. Typically, hot weather and sunlight tend to be beneficial while colder weather has the opposite affect. Skin trauma can also lead to psoriatic lesions known as the Koebner Phenomenon. Infections, stress, and drugs such as beta blockers or lithium have also been known to exacerbate psoriasis.

Page 66: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Psoriasis Treatment Continued

Topical therapy:

•  Anthralin •  Vitamin D3 analogs (Calcipotriene) •  Tazarotene •  Topical glucocorticoids •  Emollients •  Tar preparations •  Salicylic acid •  Ultraviolet light

•  Narrow Band Ultraviolet B •  Psoalen plus Ultraviolet A (PUVA)

Systemic therapy:

•  Methotrexate •  Cyclosporine •  Retinoids •  Systemic glucocorticoids

Other:

•  Etanercept (TNF – alpha receptor) •  Infliximab (monoclonal antibody against TNF-alpha)

Page 67: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Psoriasis Treatment Continued

Topical therapies are commonly used to treat psoriasis, typically if less than twenty percent of the body is involved. All patients should incorporate routine emollient use in their management of psoriasis. Keratolytic agents, such as salicylic acid or tar preparations are used to soften the skin and help remove the scales. Topical glucocorticoids are very effective in reducing erythema, pruritus and scaling; but for long term effects, these agents are limited to specified times for use. Tazarotene and calcipotriene, although different, both affect the epidermal cell proliferation abnormality of psoriasis.

In moderate psoriasis, systemic immunosuppressants such as cyclosporine, have been used with good results. Other agents that can be used include systemic glucocorticoids, methotrexate, and retinoids.

Researchers have discovered that people with psoriasis often have increased levels of TNF in their affected skin areas. These increased levels of TNF can overwhelm the immune systems ability to control the inflammation of psoriasis. Agents like etanercept and infliximab bind and deactivate some TNF molecules before they can trigger inflammation. By interrupting the chain of events that leads to inflammation, these agents can work the immune system to help reduce inflammatory symptoms.

The FDA in May of 2003 approved etanercept for moderate to severe plaque psoriasis. Based on two phase III studies evaluating more than 1200 patients with moderate to severe psoriasis demonstrating that psoriasis patients may be able to speed their clearing time at a higher dose and then maintain it at a lower dose. Patients received placebo, or etanercept 25 mg twice weekly or 50 mg twice weekly for 12 weeks. Patients then continued treatment for an additional 12 weeks, but those who were given 50 mg initially were "stepped down" to 25 mg twice weekly.

Of those given the 50 mg loading dose and then stepped down, nearly half (47 percent) achieved 75 percent improvement in their psoriasis score. In psoriasis studies, many patients experienced clinical improvement as early as four weeks or up to a few months after starting etanercept. However, these agents can weaken the immune system thereby increasing the likelihood of infection. Therefore caution is advised for the elderly due to the already increased risk of infection for this age group.

Page 68: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Rosacea

Etiology: multifactorial; vascular disturbance and possibly mites Triggers: alcohol, chemicals, sun exposure, trauma, changes in temperature, spices

Signs & Symptoms:

•  Erythema •  Easy flushing •  Telangiectasias •  Papules •  Pustules

Complications:

•  Rhinophyma •  Blepharitis, corneal involvement

Examples:

•  Rhinophyma •  Acne Rosacea •  Drug Reactions – Acne Rosacea

Rosacea, which typically results in flushing and blushing, is a relatively common disease occurring more commonly in fair-skinned people.

Though common throughout adulthood, rosacea peaks between the ages of 40 and 50. Women are more frequently afflicted, but men more readily develop the tissue and sebaceous gland hyperplasia that lead to complications.

Although its precise etiology is unknown, there are many factors that contribute to rosacea. One known risk factor for developing rosacea is sun-damage.

Families with a history of rosacea should take extra precaution from the sun. Additionally, evidence suggests a circulatory disturbance in the facial vascular system, as well as a possible inflammatory reaction to demodex folliculorum mites.

Patients with rosacea also experience a flare or trigger of the condition with such factors as alcohol, chemicals, sun exposure, changes in temperature, spices, and trauma.

Page 69: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Rosacea

There is a wide spectrum of rosacea manifestations. Acne and rosacea can coexist, and certainly other types of rosacea are possible. Patients typically present with a generalized erythema (redness) around the nose and cheek region of the face.

At times, this can spread to a V-neck region of the chest. Typical lesions may include papules or pustules, thus resembling acne. Telangiectasias, or spider like veins can also be present. Most patients complain of developing sensitive skin changes that react with fragrances, cosmetics, and other skin care products.

In more serious cases, large inflammatory nodules and tissue hyperplasia can occur. Ultimately, this can result in a physical deformity of the nose called rhinophyma. Ophthalmic changes with blepharitis and conjunctivitis can also occur.

Page 70: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Nonpharmacological Treatment of Rosacea

•  Avoid alcohol, hot beverages, and spicy foods •  Proper sun protection •  Avoid extremes of temperature •  Avoid hot baths, high humidity, extreme exercise •  Avoid certain drugs •  Minimize stress

Rosacea is a treatable disease. Because there are triggers that exacerbate this condition, nonpharmacological management of rosacea is important. Patients with rosacea should be advised to avoid alcohol, hot beverages, and spicy foods.

Also to be avoided are very hot or very old climates, hot baths, high humidity, vigorous exercise, and skin care products which produce flare-ups. Probably most important is vigilant sun protection. As patients with rosacea have skin that is unusually vulnerable to chemical and physical insults, great care should be taken in selecting soaps, cleansers, lotions, make-up, and sunscreens.

Page 71: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Pharmacologic Treatment of Rosacea

Topical:

•  Metronidazole 0.75% or 1% cream, gel, or lotion applied once to twice daily. Can be used as monotherapy or with oral antibiotics

•  Erythromycin or clindamycin topicals are sometimes used and may be effective •  Topical glucocorticoids should be avoided

Systemic:

•  Tetracyclines (incl. minocycline, doxycycline) are quite effective in controlling rosacea and reducing erythema (may be titrated to patient response)

•  Metronidazole 500mg by mouth twice daily can be used as a second-line therapy when other methods have failed •  Macrolides (erythromycin, clarithromycin, or azithromycin) can be used as well •  Low dose clonidine or non-specific beta-blockers may be used for control of flushing

Page 72: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Pharmacologic Treatment of Rosacea

Depending on its severity, rosacea can be controlled with various topical and oral agents. Typically in milder cases, topical metronidazole seems to keep rosacea in remission.

It is available as a 0.75% gel or lotion, typically applied twice daily. The 1% cream is applied once daily. Topical metronidazole has its greatest effect on papules and pustules, and reducing erythema. It has less effect for telangiectasias or flushing. This can be used as monotherapy or in conjunction with oral antibiotics.

Rosacea responds very well to oral antibiotics. Tetracyclines are most commonly used, in full doses. If these are ineffective or not tolerable, macrolides such as erythromycin, azithromycin, or clarithromycin can be used. Oral antibiotics can be ‘titrated’ to its lowest effective dose for long term use.

Telangiectasias do not respond well to antibiotics but can be treated with laser treatments. Rhinophyma needs to be surgically treated.

Page 73: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Fungal Skin Infections

Common Fungal Infections

•  Trichopyton Species •  Tinea corporis •  Tinea cruris •  Tinea pedis

Infections with Tinea species, also known as dermatomycosis, are the most common skin infections. Tinea corporis can occur anywhere on the body with the exceptions of the scalp, feet, hands, or beard.

It presents with annular plaques which are often scaly. Tinea corporis is also known as ringworm. Tinea cruris, or jock itch, usually appears in the groin area and usually spares the genitals. Tinea pedis affects the feet and is the most common dermatophyte infection. Tinea pedis is also known as athletes foot and usually presents with a toe web maceration.

Page 74: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Tinea Infections

Available Treatments

•  Tolnaftate (Tinactin® •  Ketoconazole (Nizoral® •  Clotrimazole (Lotrimin® •  Terbinafine (Lamisil® •  Econazole (Spectazole® •  Nystatin powder

Treatments usually need to be applied once to twice daily. Tinea Corporis and Tinea Cruris generally have a 2 week treatment while Tinea pedis typically requires a 4 week course. Non-pharmacologic treatments involve avoiding moisture. Patients should be counseled to dry unaffected areas of the body before affected areas to avoid spreading and to wear loose fitting clothing to avoid further irritation. Topical steroids can be added to the treatment protocol if there is significant inflammation involved.

Page 75: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Additional Resources

http://www.dermnet.com

http://www.dermatlas.com

Blount BW, Pelletier A. Rosacea: A common, yet commonly overlooked, condition. Amer Fam Physician 2002;66(3):435-440.

DeSimone EM, Hagge KM. Current therapy of seborrheic dermatitis. US Pharmacist 1998;23(4):67-75.

Federman D, Hogan D, Taylor R, Caralis P, Kirsner RS. A comparision of diagnosis, evaluation and treatment of patients with dermatological disorders. J Am Acad Dermatol 1995;32:726-729.

Greaves MW, Weinstein GD. Treatment of psoriasis. NEJM 1995;332:581-588.

Haddad AR, Oishi T, Kuniyki T. Pruritus in the elderly. US Pharmacist 1996;21(4):58-65.

Henderson ML. Contact dermatitis: a common problem. US Pharmacist 1998;23(4):76-80.

Page 76: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Additional Resources

Kurban RS, Kurban AK. Common skin disorders of aging: diagnosis and treatment. Geriatrics 1993;48(4):30-42.

Litt JZ. Rosacea: how to recognize and treat an age-related skin disorder. Geriatrics 1997;52(11):39-47.

MacDonald A, Burden AD. Psoriasis: advances in pathophysiology and management. Postgrad Med 2007;83:690-697.

National Skins Center’s Information on Common Skin Diseaseshttp://www.nsc.gov.sg/showpage.asp?id=76 Norman RA. Xerosis and pruritus in the elderly: recognition and management. Dermatologic Therapy 2003;16:254-259.

O’Dell, M.L. Skin and Wound Infections: An Overview. American Family Physician 1998;57,10 2424-32.

Pariser DM. Topical steroids: a guide for use in the elderly patient. Geriatrics 1991;46(10):51-63.

Bonifati C, et al. Recognition and treatment of psoriasis: special considerations in the elderly. Drugs Aging 1998;12(3):177-190.

Reddy M. Skin and Wound Care: Important Considerations in the Older Adult. Advances in Skin & Wound Care 2008;21(9):424-436.

Schwartz RA, Janusz CA, Janniger CK. Seborrheic Dermatitis: An Overview. AAFP 2006;74:125-130.

Weinstein, A., Berman, B., Topical Treatment of Common Superficial Tinea Infections. American Family Physicians 2002;65(10) 2095-2102

Page 77: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Vascular Lesions, Blistering Diseases and Neoplasms

Learning Objectives

By the end of this Review Concept you should be able to:

• Compare and contrast the clinical features of various vascular lesions, including cherry and spider angiomas, venous lakes, angiokeratomas de Fordyce and actinic purpura.

• Describe the pathogenesis, clinical features and recommended pharmacologictreatment of bulbous pemphigoid and pemphigus vulgaris.

• Describe the pathogenesis, clinical features and recommended treatment ofseborrheic keratoses.

• Identify symptomatic differences of basal cell, squamous cell and melanoma.

Page 78: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Common Vascular Lesions

•  Cherry Angiomas •  Spider Angiomas •  Venous Lakes

Characteristics:

•  Asymptomatic •  Treatment optional, with electrodessication or laser surgery

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=-960745285

Cherry Angioma: 2-4 mm red dome shape papules

A 62 year old man complained of increasing numbers of cherry angiomas on the trunk and extremities.

Some of the larger lesions had bled with scratching. Many of the lesions were quickly ablated with pulsed dye laser therapy.

Page 79: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Common Vascular Lesions

Changes in the vascularity of the skin account for many of the vascular lesions seen in the elderly.

Benign lesions such as cherry angiomas are extremely common. They appear as deep red, well-demarcated papules, primarily on the trunk, and have no clinical significance.

Spider angiomas, which appear on the face neck and arms, are characterized by visible blood flow through a raised arteriole and radiating capillaries. They may be associated with changes in estrogen secretion.

Venous lakes are dark blue, compressible, slightly raised vascular lesions found predominantly on the ear or lip. The dilated, blood-filled, thin-walled venules that compose these venous lakes may bleed following minor trauma, but are otherwise of no clinical significance.

Electrodesiccation and laser surgery are recommended for removing these kinds of lesions.

Page 80: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Angiokeratomas of Fordyce

•  Involves the scrotum •  Usually asymptomatic •  May produce itching, pain or bleeding •  Treatment optional

Nitrogen cryotherapy Electrodessication Laser surgery

Local venous hypotension may play a role in Angiokeratomas of Fordyce, a benign skin disorder that affects nearly twenty percent of men over seventy years of age. It is characterized by dilation of superficial dermal blood vessels and hyperkeratosis of overlying epidermis of the scrotum.

The papules are one to four millimeters in size, bright red to purple in color. They become larger, darker, and more numerous with age. While they are usually asymptomatic, patients sometimes may complain of itching, pain or bleeding.

An important differential diagnosis is angiokeratoma corporis diffusum or Fabrey’s disease, which is associated with renal failure in younger men. Nitrogen cryotherapy, electrodessication and laser surgery are optional treatment modalities.

Source: http://dermnet.com/image.cfm?imageID=20808&moduleID=20&moduleGroupID=589&groupindex=1&passedArrayIndex=13

Angiokeratomas of Fordyce: multiple 1-4 mm purple papules

Page 81: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Actinic Purpura

Actinic Purpura

•  Asymptomatic •  May persist for many weeks •  No effective treatment

Actinic Purpura

Source: http://www.skinsite.com/info_bateman%27s_purpura.htm

Actinic purpura is a weakening of the perivenular connective tissue by chronic sun exposure.

The purpura occurs primarily on exposed areas such as the forearm. Lesions are irregularly shaped and fairly well demarcated violaceous. They are usually red-brown macules, varying in size from a few millimeters to several centimeters.

They are asymptomatic, but may persist or many weeks. There is no effective treatment however topical application of alpha hydroxyacid may be beneficial. Medications that thin the blood, such as aspirin, may contribute to the development of this disorder.

Page 82: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Bullous Pemphigoid

Etiology: Idiopathic IgG autoimmune reaction Separation of basal keratinocytes from basal membrane

Common sites: Trunk, groin, forearms

Signs/Symptoms: Large, tense bullae on erythematous base Intense pruritus Possible oral involvement

Duration: Several months to a few years

Bullous Pemphigoid

http://www.dermnet.com/image.cfm?imageID=1151&moduleID=5&moduleGroupID=64&groupindex

Page 83: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Bullous Pemphigoid

In addition to vascular lesions, the elderly are susceptible to blistering diseases such as bullous pemphigoid and pemphigus vulgaris.

The more common of the two is bullous pemphigoid, an immunologically mediated idiopathic disease that is characterized by large, tense bullae arising on normal skin or plaques. They tend to appear on an erythematous base. Body sites most frequently affected include the trunk, groin, axilla and flexor surfaces of the forearms.

Clinical features include intense pruritus and possible oral involvement. Although most cases seem to occur without obvious factors, there are several reports of bullous pemphigoid being precipitated by ultraviolet light or radiation therapy.

The disease is self-limited, lasting from several months to a few years. However, as high as ten to twenty percent of cases result in fatality either from the disease itself or from complications of therapy. Almost half of patients develop an elevated total serum IgE, and blood eosinophilia.

Page 84: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Bullous Pemphigoid

Mild to Moderate Cases: Potent topical corticosteroids (e.g., prednisone 20 – 60 gm daily)

Severe Cases:

Prednisone 60 – 100 mg by mouth daily

Azathioprine 50 – 150 mg daily

Sulfapyridine 1 – 4 gm daily

Dapsone 100 – 300 mg daily

Methotrexate 25 – 35 mg weekly, by mouth or intramuscularly

Cyclophosphamide 2 – 3 mg/kg/day initially with maintenance dose of 100 gm/day

Cyclosporin 3 – 10 mg/kg/day by mouth

Page 85: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Bullous Pemphigoid

In the absence of contraindications, oral prednisone should be started at doses of sixty to one hundred milligrams per day, with rapid tapering once blisters have stopped forming and complete discontinuation once remission is achieved.

Immunosuppressive agents such as azathriopine may be substituted, but require six to eight weeks of treatment for full benefit.

As a result, the steroid dosage cannot be reduced immediately. Side effects of immunosuppressants include risk for infection, bone marrow depression and hepatotoxicity.

Dapsone-induced adverse effects, such as methemoglobinemia, dapsone syndrome and agranulocytosis, are deterrents to its use. Dapsone may be more effective than sulfapyridine. Cyclosporin and etretinate may be of benefit in pemphigus, but are not effective in all cases.

Page 86: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Pemphigus Vulgaris

Etiology:

•  IgG autoimmune reaction •  Separation of keratinocytes within

the epidermis

Common sites:

•  Neck, scalp, face, groin, axilla, mucous membranes

Signs/Symptoms:

•  Flaccid bullae •  Oral erosions •  Nikolsky sign

Pemphigus Vulgaris

Source: http://www.dermnet.com/image.cfm?imageID=1250&moduleID=5&moduleGroupID=73&groupindex=0&passedArrayIndex=8

Page 87: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Pemphigus Vulgaris

Pemphus Vulgaris: vesicles and bullae, some with crusts and erosions

This 35 yr old man had gradually progressive vesicles and bullae on the torso and scalp for 6 months. Aggressive therapy with oral corticosteroids brought the lesions under control within 1 month.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=987801988

Page 88: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Pemphigus Vulgaris

Pemphigus vulgaris is another autoimmune, life-threatening skin disorder that afflicts men and women between forty and sixty years of age. It is characterized by flaccid, rather than tense, bullae and erosions of the neck, scalp, face, groin, and axillae. Mucous membrane lesions are common, and oral erosions are the presenting sign in sixty percent of patients. Almost all mucous membranes are involved.

Firm, lateral pressure on the skin surface may produce Nikolsky sign. By pressing on the unaffected skin, the bullae can be extended laterally, a finding referred to as Nikolsky's sign. The mortality rate is as high as twenty-five percent. Pemphigus-like adverse drug reactions have been associated with penicillamine, angiotensin-converting enzyme inhibitors such as captopril, and enalapril as well as nifedipine..

Page 89: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Pemphigus Vulgaris

Prednisone •  60 – 80 mg by mouth daily

Azathioprine •  1.5 – 3 mg/kg/day (maximum 250 mg); decrease to 1-2 mg/kg with marked improvement

Methotrexate •  25 – 35 mg weekly by mouth or intramuscularly

Cyclophosphamide •  100 – 200 mg daily

Dapsone •  100 – 300 mg daily

Gold salts •  25 mg intramuscularly initial dose

Rituximab •  375mg/m2 weekly for 4 weeks

Burrow’s solution and silver sulfadiazine 1% cream for pain and secondary infection

Page 90: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Pemphigus Vulgaris

Treatment of pemphigus vulgaris is similar to that for bulbous pemphigoid. Starting doses of sixty to eighty milligrams of prednisolone are recommended, with the possibility of much higher doses to suppress new blister formation.

Azathioprine combined with corticosteroids has been reported to be highly effective in the treatment of severe, generalized pemphigus vulgaris, providing long-term remissions and possibly cures in most patients.

An initial dose of cyclophosphamide of one hundred to two hundred milligrams per day has been recommended in pemphigus patients, and in many cases this dose may be tapered to one hundred milligrams after three weeks. Cyclophosphamide is recommended over methotrexate as adjunctive therapy due to its activity on B cells.

For the treatment of pemphigus, methotrexate has been administered intramuscularly or orally as a single weekly dose or as three doses administered over a thirty-six-hour period. However, because methotrexate has not been effective in controlling acute episodes of pemphigus, it is not a substitute for prednisone.

Patients with mild pemphigus have been successfully treated with dapsone, however, treatment failure is often encountered. Either gold sodium thiomalate or gold thioglucose has been used with or without steroid therapy.

Page 91: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Pemphigus Vulgaris

The initial dose is twenty-five milligrams intramuscularly, followed by subsequent weekly doses of fifty milligrams.

Following clinical improvement, the drug can be administered every two to four weeks.

For refractory patients, rituximab may be considered due to its reduction of plasma cell expression. Patients on these therapeutic regimens should always be closely monitored for adverse renal and hematologic effects as well as signs and symptoms of infections. Infection can be a serious complication of the treatments of pemphigus vulgaris.

Page 92: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Seborrheic Keratosis

Signs and Symptoms

•  Tan to brownish-black lesions •  Rough Surface •  Most commonly found on the trunk •  Often asymptomatic but easily irritated

Treatment

•  Cryosurgery with liquid nitrogen •  Curettage •  Excision

•  Biopsy •  Shave

A 77-year-old man was evaluated for an enlarging warty growth on the scalp for 10 years. A biopsy confirmed the diagnosis of a giant seborrheic keratosis

Source: http://www.dermatlas.com/derm/IndexDisplay.cfm?ImageID=91774460

Seborrheic keratosis consists of hyperkeratonic lesions of tan to dark brown pigmentation. This condition is generally asymptomatic, however it can become irritated and painful. Treatment is generally for cosmetics or to reduce irritation. Because seborrheic keratosis is difficult to distinguish from melanoma, biopsy excision should be used if there is clinical suspicion of malignancy.

Page 93: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Benign and Malignant Neoplasms

Benign and malignant neoplasms are another class of skin disorders that afflict the elderly with greater frequency. Actinic keratoses are related to ultraviolet radiation exposure, and therefore best prevented by avoidance of the sun and cumulative exposure. Lentigines are lesions caused by an increase in the melanocyte number and melanocyte pigmentation and they resemble a freckle. Solar lentigo is the term used to describe age spots and occur more frequently in areas of the body exposed to the sun.

Other benign lesions include acrochordons, flesh-colored or pigmented lesions commonly occurring on the neck, axillae and trunk, and keratoacanthomas, rapidly enlarging nodules that have a smooth outline and a central keratin plug. It is sometimes difficult to differentiate a keratoacanthoma from squamous cell carcinoma.

Page 94: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Actinic Keratoses

Common sites: •  Sun-exposed areas: head, neck, forearms, dorsal hands

Signs/Symptoms: •  2 to 6mm erythematous, flat, scaly papules

Treatment: •  Cryosurgery with liquid nitrogen •  Curettage •  Topical 5-fluorouracil twice daily for 2 – 4 weeks •  Imiquimod topical cream applied once daily

2 – 3 days per week for 16 weeks •  Diclofenac 3% gel applied twice daily for 90 days

Actinic Keratoses: multiple symmetric scaly papules and brown macules

This elderly woman had sand paper like papules and brown macules scattered over sun exposed areas of her arms, face, and neck.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=-1479818130

Page 95: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Actinic Keratoses

Actinic keratoses (AKs) are cutaneous neoplasms of epidermal keratinocytes that develop due to prolonged ultraviolet radiation exposure. AKs are the third most common reason for patients to see a dermatologist. As AKs are related directly to cumulative sun exposure, it is typically present on the head, neck, forearms, and dorsal hands.

If left untreated, AKs can be a precursor to squamous cell carcinoma, and thus patients at high risk should receive routine follow up. Of the available treatments available, there is about a 90% cure rate.

The most common treatment is with cryosurgery with liquid nitrogen. This is applied and the area of the skin which is lowered to approximately -50 degrees. Curettage is also a common mode of therapy. Another frequently used treatment is with topical 5-fluorouracil, which is applied to the affected region twice daily for 2 to 4 weeks.

Also available are imiquimod and diclofenac topical products. Patients should be adequately informed of the discomfort, pruritus, burning, and erythema that can be expected with these therapies.

Page 96: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Epidemiology and Clinical Presentation of Basal Cell Carcinoma

Epidemiology: •  75%of all diagnosed skin cancer •  99% of patients are white, 95% between 40 and 70 yo

Risk factors: •  UV exposure

Common sites: •  Head and neck

Clinical Presentation: •  Solitary or multiple •  Pigmented or cystic •  Slow growing •  Translucent border •  Dome-shaped

Basal Cell Carcinoma: 1.5 cm pearly translucent nodule with overlying telangiectasias and crusting

A 68-year-old man was evaluated for a pearly translucent nodule on the right ear for 2 years. A skin biopsy confirmed the diagnosis of basal cell carcinoma, and the nodule was excised by a Mohs surgeon.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=-290660217

Page 97: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Epidemiology and Clinical Presentation of Basal Cell Carcinoma

Of malignant neoplasms, basal cell carcinoma is the most common. More than ninety-nine percent of patients are white, and ninety-five percent are between the ages of forty and seventy-nine. Ultraviolet light exposure is the most important risk factor.

Transplant patients who receive immunosuppressive therapy are also at a much higher risk than the general population. The majority of tumors occur in the head and neck area, with nearly a quarter on the nose alone.

Basal cell carcinoma presents as firm, round to oval lesions, with a rolled border of “pearly” papules and fine telangiectasia. The center may have a crust or ulceration. Lesions may be solitary or multiple, pigmented or cystic.

Page 98: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment Options for Basal Cell Carcinoma

Central Face Lesions: •  Mohs microscopically controlled surgery •  Primary excision •  Cryotherapy •  Ionizing radiation •  Experimental: intralesional interferon, photodynamic therapy

Other Lesions: •  Electrodesiccation •  Curettage •  Topical flurouracil •  Topical imiquimod

Ongoing: •  Daily use of sunscreen, follow-up visits •  Oral Retinoid treatment

Although slow-growing and rarely metastatic, basal cell carcinoma may produce extensive tissue damage if neglected. The size and location of the tumor determines the best treatment. While recurrence is less than four to six percent, one-third of all patients with basal cell carcinoma develop a second primary tumor. For this reason, routine follow-up visits are recommended for at least five years after treatment.

Page 99: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Clinical Picture of Squamous Cell Carcinoma

Risk factors: •  UV exposure •  Inorganic arsenic •  Chronic radiation dermatitis •  Human papillomavirus •  Sinus tracts •  Chronic burn scars •  Leg ulcers •  Actinic Keratosis lesions

Common sites: •  Sites of scarring or chronic inflammation, sun exposed areas in the absence of predisposing factors

Clinical Presentation: •  Variable (scaled, ulcerative, nodular and fungating) •  Appear as solitary keratitic nodules •  Lesions on unexposed areas may be signs of metastases

Page 100: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Clinical Picture of Squamous Cell Carcinoma

Squamous Cell Carcinoma

Source: http://www.dermnet.com/image.cfm?imageID=19893&moduleID=12&moduleGroupID=355&groupi

ndex=0&passedArrayIndex=10

The second most common form of skin cancer is squamous cell carcinoma. In addition to ultraviolet light, predisposing factors include chronic radiation dermatitis, human papilloma virus, burn scars and leg ulcers. Immunosuppressed patients have an incidence five to twenty times greater than the general population. Actinic keratoses are precursor to squamous cell carcinoma, as are the sharply demarcated, red-pink scaly plaques of Bowen’s disease. Invasive squamous cell carcinoma appears as an indurated, well-demarcated, erythematous, scaly plaque. It tends to occur at sites of scarring or chronic inflammation rather than sun-exposed areas.

Page 101: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Treatment Options for Squamous Cell Carcinoma

•  Mohs microscopically controlled surgery •  Electrodesiccation •  Curettage •  Primary excision •  Cryotherapy •  Systemic retinoids •  Ionizing radiation

For metastatic disease: •  Radiation or chemotherapy

For ongoing prevention: •  Daily use of sunscreen, follow-up visits

Because of the risk of recurrence or metastasis, treatment of the primary lesion must be thorough. Also, a sentinel lymph node biopsy should be done to rule out metastasis. Treatment options include microscopically controlled surgery, electrodesiccation and curettage. Diligent follow-up is essential.

Page 102: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Melanoma

Epidemiology: •  Increase in overall incidence and death rates for elderly since 1960

Risk factors: •  Family history, skin types I & II, atypical nevi, advanced age, intermittent UV exposure, tendency to burn rather than tan

Assessment: •  The A, B, C, D, E’s of skin cancer prevention

•  Check for Asymmetry, Border irregularity, Color variegation, Diameter > 6 mm, Elevation from the surface

Survival Rate: •  Stage I: > 99% for 8 years •  Stage IV: 35% for 8 years

Melanoma

Source: http://www.dermnet.com/image.cfm?imageID=20588&moduleID=14&moduleGroupID=427&groupindex=0&passedArrayIndex=6

Page 103: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Melanoma

Main Types of Melanoma

•  Superficial spreading melanoma •  Nodular Melanoma •  Lentigo melanoma •  Acral Melanoma

Malignant Melanoma: Look for the A, B, C, Ds -black irregularly bordered and textured plaque

A 69 year-old-man was evaluated for an expanding pigmented plaque on the left ear. Histology revealed a superficial spreading melanoma with a Breslow index of 0.55mm. No metastases were noted on physical examination, and the scar was re-excised with a 1 cm margin.

Page 104: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Melanoma

Malignant melanoma is a melanocytic disorder.

Incidence rates have risen dramatically in the last forty years, and age-adjusted death rates in the elderly have increased. Risk factors include a family history of the disease, white skin, and advanced age. Malignant melanoma can occur anywhere on the skin and is often seen on the back and lower extremities.

Any patient with a changing mole or pigmented lesion should be evaluated for melanoma using the following criteria: asymmetry, border irregularity, color variegation or diameter greater than six millimeters. Survival rates are based on subsequent staging.

Stage I disease involves local disease has an eight-year survival rate of greater than ninety-nine percent.

Stage II and Stage III involve a larger tumor mass and/or lymphatic spread. Stage IV involves distant metastasis and its eight-year disease-free survival rate is only thirty-five percent.

Page 105: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Management of Melanoma

Stage I: •  Early detection with biopsy •  Surgical excision

Stage II, III: •  Interferon-alfa-2b

Stage IV: •  Recombinant interleukin-2 •  Combination therapy •  Chemotherapy

•  Dacarbazine •  Cisplatin •  Carmustine

Since other disorders can mimic the appearance of melanoma, accurate diagnosis depends on a biopsy.

Early detection and excision of Stage I melanoma is the current treatment of choice. At this time, interferon-alfa-2b is the only systemic agent in locally advanced melanoma that has demonstrated a role as therapy after surgical treatment. This agent was found to be beneficial in some patients with Stage II and Stage III disease as adjuvant therapy after surgery.

Treatment for patients with Stage IV disease involves chemotherapy, immunotherapy, or a combination of both approaches.

For patients with Stage IV disease, dacarbazine is the only chemotherapeutic agent that is FDA-approved for the treatment of metastatic melanoma.

Aldesleukin, a recombinant interleukin-2, has recently also been approved for the treatment of metastatic melanoma. Interleukin-2 is a glycoprotein that activates a number of the effector cells of the immune system and stimulates the secretion of various other cytokines.

The most severe adverse reaction associated with its use is a dose-related capillary leak syndrome.

Page 106: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Kaposi’s Sarcoma

Appearance: •  Purple or dark blue macules that slowly enlarge to become nodular or to form ulcers

Risk Factors: •  Predisposition in elderly men of European ancestry •  Associated with diabetes mellitus, AIDS, increased incidence of lymphoma, HSV-8 infection

Treatment: •  Klein regimen, (vinblastine titered against WBC) •  Surgical removal of severely affected areas •  Conventional and megavoltage radiotherapy •  Multiple chemotherapeutic agents •  Nonspecific immunotherapy •  Cessation of immunosuppressive therapy

Kaposi’s Sarcoma

Source: http://www.dermnet.com/image.cfm?

imageID=21028&moduleID=20&moduleGroupID=597&groupindex=3&passedArrayIndex=41

Page 107: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Kaposi’s Sarcoma

Kaposi’s sarcoma is a vascular neoplasm that primarily affects immunosuppressed individuals and is typically associated with AIDS. It occurs most commonly in elderly men of Central European ancestry. Lesions typically appear on the distal lower extremities as firm, violaceous, or bluish-black coalescing maculas and plaques.

The disease progresses slowly, sometimes involving the GI tract. It may coexist with Hodgkin's or non-Hodgkin's lymphoma. Treatment is based on the extent of the disease and most elderly patients with Kaposi’s sarcoma do well.

The Klein regimen, using vinblastine titered against the white blood cells, is an effective treatment. Other management modalities for Kaposi’s sarcoma include nonintervention, surgical removal of severely affected areas, conventional and megavoltage radiotherapy, multiple chemotherapeutic agents, nonspecific immunotherapy, and cessation of immunosuppressive therapy in iatrogenically immunosuppressed patients.

In the iatrogenically immunosuppressed patient who develops Kaposi’s sarcoma, the cessation of immunosuppressive therapy may be the most effective treatment.

Page 108: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Cutaneous T-Cell Lymphoma

Appearance: •  Erythematous thin scaly patches initially in mycosis fungoides and erythrodermic and exfoliative appearance

in Sézary syndrome

Common sites: •  In mycosis fungoides, lower abdomen, groin, hips and buttocks •  In Sézary syndrome, all or almost all of the skin is erythrodermic

Risk Factors: •  Antecedent allergies •  Fungal and viral skin infections •  Sun sensitivity •  Familial aggregation of lymphoma and leukemia •  Employment in a manufacturing occupation, esp. petrochemical,

textile, metal, machinery industries

Page 109: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Cutaneous T-Cell Lymphoma

Treatment:

In mycosis fungoides: • PUVA + UV A • Topical nitrogen mustard • Topical carmustine • Topical and systemic retinoids • Total skin electron beam • Low dose methotrexate • Possibly alpha-interferon and

isotretinoin, alemtuzumab

Gemcitabine: • 1.2g/m2 IV x 3 over 1 month period

In Sezary Syndrome: • Chlorambucil 4 mg + prednisone

20 mg or methotrexate + prednisone

• Denileukin diftoxin, alemtuzumab

Multiple confluent purple 0.5-2 cm nodules some with overlying crust and scale

In 1996 this 70 year old man was diagnosed with mycosis fungoides when he developed several isolated plaques that were treated with localized electron beam.

The first course targeted the left posterior shoulder and right calf, and the second course was directed to the right wrist and left ankle. He was lesion free until June of 2002 when he developed rapidly progressive red plaques and tumors on the right forearm. A biopsy showed changes consistent with tumor stage mycosis fungoides.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=-1704732314

Page 110: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Cutaneous T-Cell Lymphoma

Cutaneous T-cell Lymphoma: generalized erythema and scale

This 72-year- old man with 1 year history of erythroderma and 3 month history of generalized pruritus, no loss of appetite or weight loss, on examination there was generalized lymphadenopathy and edema which was more of subcutaneous in nature. His blood work up initially revealed 86% lymphocytes as oppose to 2% neutrophils. LDH was 478 reasonable for aggressive

disease.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=-130614020

Page 111: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Cutaneous T-Cell Lymphoma

T-Cell Lymphoma: generalized annular and arcuate violaceous indurated plaques

This 72-year-old woman complained of persistent annular plaques for 4 months. Several lesions on her wrist ulcerated. Skin biopsies revealed a T-cell lymphoma, and special markers showed a predominance of CD4+ and CD30+ cells that extended

from the dermis into the fat and surrounded vessels and adnexal structures.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=1617593808

Page 112: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Cutaneous T-Cell Lymphoma

Cutaneous T-cell lymphoma is a malignancy of the T helper lymphocyte. The major types are mycosis fungoides, comprising about ninety percent of cases, and Sézary syndrome, the leukemic form. Cutaneous T-cell lymphoma affects men twice as often as women, and blacks twice as often as whites.

Lesions can affect any area and appear initially as a dermatitis-like patch. As the disease progresses, lesions become more plaque-like, and eventually become tumors. The median patient age for cutaceous T-cell lymphoma is sixty-six, with reduced survival rates among older adults. The prognosis depends on the extent of cutaneous lesions and the presence of lymphatic or visceral disease.

In more advance disease, the lungs, spleen, and liver are the most common visceral organs involved, but any organ is susceptible. Modalities found to be effective in treating cutaneous mycosis fungoides include oral psoralens and ultraviolet A therapy, topical nitrogen mustard or carmustine, total skin electron beam, and low dose methotrexate. Recent reports also indicate beneficial results with alpha-interferon and isotretinoin.

Newer agents to the market include alemtuzumab for refractory disease, denileukin diftoxin (a fusion between IL-2 and diphtheria toxin), which is also available for patients who have failed other therapies. The management of Sézary syndrome is generally difficult, since PUVA or topical therapy has limited effects.

A widely used regimen is combination low dose chlorambucil and prednisone. Methotrexate may be used in place of the chlorambucil. Gemcitabine 1.2 g/m2 IV over 30 minutes for three doses over a 1 month period demonstrates palliative response.

Treatment is typically well tolerated with mild hematologic toxicity and no serious nausea and vomiting. Alpha interferon and extracorporeal photochemotherapy may also have a role.

Page 113: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Resources

For additional information, see:

Antiman K, Chang Y. Kaposi’s Sarcoma. NEJM. 2000;342(14):1027-1038.

Federman D, Hogan D, Taylor R, Caralis P, Kirsner RS. A comparison of diagnosis, evaluation and treatment of patients with dermatological disorders. J Am Acad Dermatol 1995;32:726-729.

Gordon ML, Hecker MS. Care of the skin at midlife: diagnosis of pigmented lesions. Geriatrics 1997;52(8):56-68.

Kurban RS, Kurban AK. Common skin disorders of aging: diagnosis and treatment. Geriatrics 1993;48(4):30-42.

Luba MC, et al. Common Benign Skin Tumors. American Family Physician 2003;67(4):729-738.

Mcintyre WJ, et at. Treatment Options for Actinic Keratosis. American Family Physicians 2007;76(5):667-671.

Mihai S, Sitaru C, Immunopathology and molecular diagnosis of autoimmune bullous disease. Journal for Cellular and Molecular Medicine 2007;11(3):462-481.

Rosen ST, Querfeld C. Primary Cutaneous T-Cell Lymphomas. Hematology 2006;323-330.

Schwartz RN. Melanoma: the expanding role of the pharmacist. US Pharmacist 1998;64(6):65-72.

Shelton R. Skin Cancer: A Review and Atlas for the Medical Provider. The Mount Sinai Journal of Medicine 2001;68(4&5):243-252.

Page 114: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Resources

Stulberg D, Clark N, Tovey D, Common Hyperpigmentation Disorders in Adults: Part II. American Family Physician 2003;68(10):1964-1968.

Wong CSM, Strange RC, Lear JT. Basal Cell Carcinoma. BJM 2003;327:794-798.

Page 115: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Drug-Induced Skin Disorders

Learning Objectives

By the end of this Review Concept you should be able to:

• Compare and contrast various types of drug-induced skin eruptions in terms of presenting features and medications commonly implicated in causing such reactions.

• List common local and systemic signs and symptoms which signal a serious or life-threatening drug-induced adverse skin reaction.

Page 116: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Drug-induced Inflammatory Skin Disorders

•  Affect 3% of hospitalized patients •  0.1% hospitalized patients have a serious skin reaction •  Elderly patients are at higher risk

Drug reaction: erythema and bulla formation

A 75-year old man with prostate cancer developed bullae on his palms associated with painful erythema and burning shortly after receiving docetaxel chemotherapy.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=-924369796

According to the World Health Organization (WHO), adverse skin reactions to drugs occur in three percent of hospitalized patients, many of whom are older adults. Fortunately, most of these drug eruptions are not severe, with serious cutaneous reactions causing fatalities in 0.1 to 0.3% of affected patients. However, as skin changes with age and older individuals take greater numbers of medications the likelihood of experiencing a drug-induced skin reaction increases.

Page 117: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Types of Drug-Induced Skin Eruptions

Type     Clinical  Characteris0cs    

Ur0carial     Pruri%c,  erythematous,  edematous  papules  or  plaques  

Morbilliform     Generalized  erythematous  macules  and  exanthematous  papules  

Erythema  mul0forme     Diffuse  macules  

Stevens-­‐Johnson  Syndrome  (SJS)     Mucocutaneous  disorder  with  ocular  involvement  and  disseminated  cutaneous  erup%ons  of  discrete  dark-­‐red  macules  

Toxic  Epidermal  Necrolysis  (TEN)     Rapid,  progressive  loss  of  the  epidermis  

Page 118: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Types of Drug-Induced Skin Eruptions

Type     Clinical  Characteris0cs    

Hypersensi0vity  Syndrome     Severe  reac%on  involving  skin  rash,  fever,  hepa%%s,  arthalgias,  lymphadenopathy  and  hematological  abnormali%es  

Vasculi0s     Inflamma%on,  necrosis  of  blood  vessels  

Serum  sickness     Type  III  hypersensi%vity  reac%on  

Angioedema     Immediate  hypersensi%vity;  symptoms  range  from  simple  ur%caria  to  anaphylaxis  

Fixed  drug     Sharply  demarcated  oval  lesions  

Photoallergic     Appear  as  solar  ur%caria  or  as  eczematous  or  lichenoid  derma%%s  on  areas  of  sun  exposure  

Phototoxic     Resembles  exaggerated  sunburn  and  is  associated  with  burning  sensa%on,  erythema,  edema  

Page 119: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Types of Drug-Induced Skin Eruptions

Hives: Well defined edematous red round annular and geographic plaques

A 24-year-old man developed hives on the second day of treatment of a respiratory tract infection with oral amoxicillin. He had similar episodes of urticarial while taking oral amoxicillin a year earlier. The wheals changed from minute to minute and

cleared 3 days after discontinuation of the antibiotic.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=1054556571

Page 120: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Types of Drug-Induced Skin Eruptions

Morbilliform eruption: symmetric 2 – 3 purpuric papules

A 34-year-old woman developed widespread purpuric papules on her legs following the ingestion of ibuprofen. The eruption resolved over a week after discontinuation of the medication.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=-1921427205

Page 121: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Types of Drug-Induced Skin Eruptions

Erythema multiforme: symmetric annular violaceous papules and plaques with dusky centers

These two pictures represent the same elderly woman who developed recurrent violaceous plaques with dusky centers on her arms and legs and erosions on her lips with a few on the palate. Although the cause was not clear, an oral hypoglycemic

agent was suspected.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=1090799846

Page 122: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Types of Drug-Induced Skin Eruptions

Toxic Epidermal Necrolysis (TEN): generalized erythema and erosions

This young woman with HIV infection on nevirapine developed progressive erythema, erosions, and skin sloughing over 2 weeks. A Nikolsky sign could be readily demonstrated.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=-2073165787

Page 123: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Types of Drug-Induced Skin Eruptions

Stevens-Johnson syndrome (SJS): widespread red papules and plaques, many with central erosions, and erosions of the conjunctivae, lips, and mouth

This 10 year old girl developed Stevens-Johnson syndrome after 7 days of treatment with trimethoprim-sulfamethoxazole. At this time, cutaneous lesions were still spreading and the conjunctivae, mouth, nose and genital mucous membranes were severely involved. Fortunately, over the subsequent 3 weeks, the rash and mucous membranes healed without complications.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=-1111850706

Page 124: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Types of Drug-Induced Skin Eruptions

Stevens-Johnson syndrome/erythema multiforme: widespread symmetric violaceous erythema, hyperpigmentation, and desquamation

This 15 year old mother (of a 2 month old son) with Stevens-Johnson syndrome developed widespread necrosis and necrosis of the skin, mouth, and lips. Fortunately her eye involvement was minor and healed quickly. This image was taken about 2

weeks into her course when most of the blisters were dry and she had developed widespread desquamation and hyperpigmentation. She still had persistent crusting and fissuring of her lips.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=562105118

Page 125: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Types of Drug-Induced Skin Eruptions

Toxic Epidermal Necrolysis: diffuse skin sloughing on a red edematous base

This 10-year-old boy developed a high fever, diffuse cutaneous edema, and widespread erythema and erosions of the skin and mucous membranes 3 weeks after starting phenytoin for seizures. He progressed with development of airway

involvement necessitating intubation. He died of complications a few days later.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=2033828751

Page 126: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Types of Drug-Induced Skin Eruptions

Vasculitis: symmetric confluent purpuric papules

A 30 year old construction worker developed symmetric confluent purpuric papules on the legs above the sock line after spending 8 hours in heavy boots at work. Skin biopsy showed a leukocytoclastic vasculitis. A systemic evaluation for

vasculitis failed to reveal a source. Note the sharp line of demarcation at the sock line.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=1421371127

Page 127: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Types of Drug-Induced Skin Eruptions

Angioedema: diffuse non-pitting edema

A 32 year old man with a seizure disorder developed thrombocytopenia and angioedema one week after phenytoin was started for seizure control. Angioedema resolved several days after the medication was discontinued.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=142

Page 128: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Types of Drug-Induced Skin Eruptions

Fixed Drug Reaction: multiple, well-defined, round to oval, purple, edematous plaques and bullae with surrounding erythema

This 25-year-old man presented had a one day history of multiple pruritic round to oval purple plaques with central bullae and marginal erythema on his trunk, extremities, lips and genitals following ingestion of co-trimoxazole for a respiratory tract

infection as self medication. He had a history of similar episodes many times in the past year with the lesions recurring on the same sites. Plaques healed rapidly with residual hyperpigmentation after discontinuation of the offending drug.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=1218958877

Page 129: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Types of Drug-Induced Skin Eruptions

Phototoxic drug reaction: photodistributed violaceous scaly crusted edematous patch

A 75 year old woman developed a doxycycline-induced phototoxic reaction shortly after beginning therapy for Lyme disease last summer. Unfortunately she did not receive counseling about sun avoidance or sun screen use while on the

photosensitizing drug.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=366607319

Page 130: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Types of Drug-Induced Skin Eruptions

Drug-induced skin eruptions can fall into any one of several categories. Urticarial disruptions, commonly known as “hives”, account for twenty-five percent of all drug rashes. Morbilliform drug eruptions are the most common. They are often the initial presentation of more serious reactions including toxic epidermal necrolysis or T-E-N hypersensitivity syndrome and serum sickness.

Erythema multiforme and its more severe variant, Stevens-Johnson syndrome, represent a spectrum of reactions that usually requires the elderly patient to be hospitalized. Erythema multiforme major usually occurs after infections, especially herpes simplex and mycoplasma, and has a benign course.

Vasculitis induced by drugs involves small blood vessels.

Serum sickness is a type III hypersensitivity reaction mediated by the deposition of immune complexes in small vessels, activation of complement, and recruitment of granulocytes.

Photoallergic reactions occur when an immediate humoral-mediated response, a delayed cell-mediated hypersensitivity response - or both - develop from a hapten or a complete antigen formed by photoactivation.

Phototoxic reactions result from direct cellular damage produced by the photoproducts, provided enough of the chemical and radiation are present.

Psoriasis, bullous pemphigoid, pemphigus, and alopecia are other skin manifestations of medication reactions.

Page 131: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Acute Adverse Cutaneous Reactions

Erythematous Drug Eruptions: •  Most common adverse drug reactions are exanthema or maculopapular eruptions

•  Often reported as “drug rashes” or “drug eruptions” •  Mechanism is likely immunological as a type IV delayed cell-mediated hypersensitivity reaction •  Eruptions occur between 4 and 14 days of starting a new drug therapy

•  Can occur 1 to 2 days after cessation of therapy •  Re-challenge eruptions can occur sooner

Lesions: •  Symmetric erythematous macules or papules •  Progressively become confluent •  Cover large patches of skin •  Mucous membranes not usually involved •  Pruritus or low-grade fever often

Treatment: •  Supportive •  Treating ‘through the eruption’ if drug is of essential importance (antimicrobials, HAART drugs) •  Eruption diminishes spontaneously after drug is withdrawn in most cases

Page 132: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Acute Adverse Cutaneous Reactions

Drug rashes, or drug eruptions as they are sometimes referred to as, are the most common adverse drug reactions affecting the skin.

Likely type IV delayed cell-mediated hypersensitivity reactions, erythematous drug eruptions can have an increased rate of occurrence in the presence of viral infections that include HIV or the Epstein-Barr virus. Treatment is generally supportive in nature, with removal of the suspected agent resulting in a quick, spontaneous diminishing of the skin eruption.

If, however, the drug therapy is essential for the patient, treating through the eruption can be considered under appropriate circumstances. Progression of the rash should be monitored closely in the 48 hours after identity and removal of the suspected drug.

Page 133: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Acute Adverse Cutaneous Reactions

Urticaria •  Common, transient •  Acute eruption usually associated with pruritus •  Involvement of dermal and subcutaneous tissue is known as angioedema •  Can be complicated by anaphylaxis •  Histologically non-specific •  Usually occurs within 36 hours of exposure, but can be as short as a few minutes

Angioedema •  Pale or pink swelling •  Affects the face, including mucous membranes •  Swelling is nonpitting, erythematous or skin-colored •  Rarely itching, usually painful and tender instead •  In anaphylaxis, can involve other systems leading to respiratory collapse, shock, or death

Treatment: •  Withdrawal of offending agent •  Consideration of H1-receptor blockers •  Systemic corticosteroids, IM epinephrine, and airway protection are necessary in anaphylaxis

Urticaria is a common, transient acute eruption that is typically associated with pruritus. Involvement of dermal and subcutaneous tissue is referred to as angioedema. Urticaria and angioedema are often associated, and can be complicated by anaphylaxis.

Page 134: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Photosensitivity

Accounts for as much as 8% of adverse medication-mediated adverse effects

Phototoxicity •  Not rare •  Predictable •  Can occur in any person who receives enough quantity of the phototoxic drug together with the right amount of sun

exposure

Clinical manifestations: •  Present as an exaggerated sunburn •  Followed by hyperpigmentation •  Blisters may occur (photo-onycholysis and pseudoporphyria)

Common drugs: •  Tetracyclines •  Tretinoins / retinoids •  Ketoprofen (topical) •  Quinolones •  Amiodarone •  Psoralens •  Statins •  Benzoyl peroxide •  Methotrexate •  Voriconazole •  Sulfur-containing medications •  Antimalarials

Page 135: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Photosensitivity

Photoallergy •  Cell-mediated hypersensitivity reaction •  More chronic disorder than phototoxicity •  Mainly eczematous and pruritic in nature

Clinical manifestations: •  More marked in exposed sites, but can progress outside these areas •  In the chronic phase, erythema, scaling and lichenification predominate

• Sulfur-containing medications • Quinolones • NSAIDs (including topical) • Antimalarials • Phenothiazines • Acyclovir (topical) • Pyridoxine • Ranitidine

• Pilocarpine • Fibrates • Statins • ACE inhibitors • Calcium channel blockers • Amantadine • Dapsone • Diphenhydramine • Sunscreens

Common Drugs:

Page 136: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Photosensitivity

Phototoxicity      Photoallergy  

Rela%ve  incidence   High   Low  

Dose  dependent   Yes   No  

Prior  exposure  necessary   No   Yes  

Rela%ve  amount  of  drug  required   High      Low  

Time  of  onset   Minutes  to  hours   Hours  to  days  

Clinical  appearance   Exaggerated  sunburn   Contact  derma%%s  

Histopathology   Epidermal  necrosis   Epidermal  songiosis,  dermal  inflamma%on  

Pigmentary  altera%on   Common   Uncommon  

Adapted  from:  Schein  KR  and  Scheinfeld  NS.  

Page 137: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Photosensitivity

Photosensitivity reactions are distinguished into two types: phototoxicity and photoallergy. Both oral and topical drugs can trigger photosensitive skin reactions.

Phototoxicity reactions are nearly always predictable and can occur in any patient with the right quantity of drug and sun exposure. The reaction is a result of photochemistry within the skin. Appearing as exaggerated sunburn, the clinical manifestations can progress to hyperpigmentation which is sometimes the only recognizable symptom of photosensitivity. Common drugs causing phototoxicity are provided on your screen.

Photoallergic reactions are considered to be a result of cell-mediated hypersensitivity. These reactions are typically transient, resolving after a variable length of time after the causative agent has been stopped.

Treatment for both types of photosensitivity reaction requires removal of the offending agent, and / or avoidance of sun exposure. For phototoxicity, drugs with short half-lives may be able to be given in the evening to decrease the risk of the adverse effect below the clinical threshold. For photoallergy, drug withdrawal is truly recommended because of the risk of worsening reaction with continued use or re-exposure. Topical corticosteroids and systemic antipruritic agents may also be considered.

Page 138: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Anticoagulant-induced Skin Necrosis

Warfarin •  Rare, but sometimes life-threatening effect of warfarin

•  1 in 10,000 patients exposed to warfarin will develop at onset of treatment •  Hereditary deficiency of protein C is a risk factor

•  Begins 3 – 5 days after initiation of therapy

Clinical manifestations: •  Red, painful plaques •  Evolve to necrosis, hemorrhagic blisters and ulcers

Treatment: •  Discontinuation of warfarin •  Administration of vitamin K •  Administration of heparin (if anticoagulant therapy is still warranted) •  Administration of monoclonal antibody-purified protein C concentrate

Heparin •  Can induce thrombosis and necrosis

•  In skin, and other organs •  Treatment with warfarin or antiplatelet is useful in place of heparin

Page 139: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Anticoagulant-induced Skin Necrosis

Anticoagulant-induced skin necrosis is rare, but can sometimes be life-threatening.

1 in 10,000 persons treated with warfarin will develop skin necrosis within 3 to 5 days of therapy initiation. Genetic predisposition has been identified, with those individuals deficient in protein C at greatest risk.

In the case of warfarin-induced skin necrosis, reversal of the warfarin with vitamin K and subsequent anticoagulation therapy with heparin is recommended in addition to the administration of monoclonal antibody-purified protein C concentrate.

Page 140: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

SJS and TEN •  Rare, but most severe drug-induced skin reactions

•  SJS: 1 – 6 cases / million person-years •  TEN: 0.4 – 1.2 cases / million person-years

•  Risk of developing either is increased in HIV patients •  Drugs cause 70% of cases •  Genetic susceptibility

•  Asians, Han Chinese •  HLA-B*1502 allele and SJS induced by carbamazepine •  HLA-B*5801 allele and SJS induced by allopurinol

Clinical manifestations: •  Begins within 4 weeks

•  Usually 7 – 21 days after exposure, but sometimes after drug has been withdrawn •  Occurs more rapidly with re-challenge •  Fever and signs / symptoms affecting cutaneous and mucous membranes occur 1 – 2 days before skin findings •  Skin lesions:

•  Irregularly shaped, erythematous, dusky-red, purpuric macules •  Mucous membrane involved in 85% of patients

•  Erythema and painful erosions of buccal, ocular, nasal, and genital mucosa •  Systemic manifestations:

•  Elevation of hepatic enzymes (slight), intestinal and pulmonary manifestations •  Epithelial sloughing •  Leukopenia (common) •  Eosinophilia (unusual)

• 

Page 141: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

SJS or TEN?

•  < 10% BSA, SJS •  10 – 30% BSA, SJS or TEN •  > 30% BSA, TEN

TEN: Generalized erythema and erosions

This young woman with Human immunodeficiency virus infection on nevirapine developed progressive erythema, erosions, and skin sloughing over 2 weeks. A Nikolsky sign could be readily demonstrated.

Source: http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=-234568993

Prognosis:

• SJS = 10% • TEN = 30 – 50%, secondary to sepsis or pulmonary involvement

Page 142: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

Nikolsky's sign: •  Skin condition in which the top layers of the skin slip away from the lower layers when slightly rubbed •  Positive sign is that of loose skin that slips free from the underlying layer(s) when rubbed, typically by twisting a pencil eraser against the skin

•  The area beneath is pink and moist and may be very tender. •  When the sign is positive, a blister will form in the area within minutes

Common drugs: •  Antibacterial sulfonamides •  Antiepileptic drugs •  NSAIDs •  Allopurinol •  Nevirapine

Drugs are the causative factor in 70% of cases of Stevens-Johnson Syndrome and Toxic epidermal necrolysis. HIV is a risk factor for increased incidence of SJS and TEN. With better pharmacogenomic modeling, genetic drug testing is revealing gene mutations that also increase risk for various adverse drug effects, including skin reactions. As an example, those of Asian descent with the gene mutations listed on your screen have been identified to have a 10-fold increased risk of developing SJS when exposed to carbamazepine or allopurinol, respectively, over comparator Caucasians.

Toxic epidermal necrolysis is the most serious drug-induced skin reaction, leading to death in fifty percent of cases due to sepsis. In severe cases, Stevens Johnson Syndrome can include extensive areas of epidermal necrolysis. Other systemic manifestations of TEN include mucosal lesions, impaired alimentation, photophobia, painful micturition (or painful urination) and involvement of the trachea, bronchi and gastrointestinal tract. Hypersensitivity reaction is associated with a relatively late onset and slow evolution.

Page 143: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Adverse Skin Reactions

•  Most drugs can cause erythematous eruption in 1% of users

•  The following drugs are associated with higher risk in >3% of users: •  Allopurinol •  Antiepileptic drugs •  Sulfonamide antimicrobials •  Aminopenicillins •  Cephalosporins

Page 144: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Adverse Skin Reactions

Page 145: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Adverse Skin Reactions

Many commonly used medications can be associated with adverse skin reactions.

Examples include acetaminophen, digoxin, epinephrine, and prednisone, as well as medications frequently prescribed by dermatologists. For many severe cutaneous reactions to drugs, including TEN, Stevens-Johnson Syndrome, vasculitis, and serum sickness, early recognition and intervention is essential to prevent the morbidity and mortality associated with these conditions. Once a patient experiences a serious skin adverse reaction, he or she should avoid future exposure to the offending agent.

Page 146: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Signs of Drug-Induced Adverse Skin Reactions

Page 147: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Signs of Drug-Induced Adverse Skin Reactions

To facilitate early detection and diagnosis, drug-induced skin reactions are sometimes categorized in terms of their clinical manifestations.

Eruptions may be described as macular, papular, nodular, vesicular, bullous, pustular or producing a wheal. Clinical signs that suggest a more serious drug-induced skin eruption include edema, skin pain, and palpable purpura. Systemic manifestations of serious drug-induced skin reactions include fever, swelling of the lymph nodes, and shortness of breath. Nikolsky's sign refers to apparently normal epidermis that may be separated at the basal layer and rubbed off when pressed with a sliding motion.

If any of these signs or symptoms is present, the drug should be discontinued immediately.

Page 148: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Resources

For additional information, see:

Anderson WK, Feingold DS. Adverse drug reactions clinically important for the dermatologist. Arch Dermatology 1995;131:468-473.

DeSimone EM. Dermatologic side effects of medication. US Pharmacist 1997;22(4):60-73.

Genetic test for carbamazepine-induced Stevens-Johnson syndrome. Med Letter Drugs Ther 2008;50(1284).

Federman D, Hogan D, Taylor R, Caralis P, Kirsner RS. A comparison of diagnosis, evaluation, and treatment of patients with dermatological disorders. J Am Acad Dermatol 1995;32:726-729.

Kaplan AP, Greaves MW. Angioedema. J Am Acad Dermatol 2005;53(3):373-388.

Roujeaj JC, Stern RS. Severe adverse cutaneous reactions to drugs. NEJM 1994;331:1272-1285.

Stein KR, Scheinfeld NS. Drug-induced photoallergic and phototoxic reactions. Expert Opin Drug Safety 2007;6(4):431-443.

Vassileva S, Mateev G, Parish LC. Antimicrobial photosensitive reactions. Arch Int Med 1998;158:1993-2000.

Valeyrie-Allanore L, Sassolas B, Roujeau JC. Drug-induced skin, nail, and hair disorders. Drug Safety 2007;30(11):1011-1030.

Wolf R, Orion E, Marcos B, Matz H. Life-threatening acute adverse cutaneous drug reactions. Clinics in Dermatology 2005;23:171-181.

Page 149: Module 6 - Dermatological Disorders

Copyright 2011 American Society of Consultant Pharmacists

Resources

Dermatology Image Atlas – www.dermatlas.org

MedlinePlus – http://www.nlm.nih.gov/medlineplus/ency/article/003285.htm