Dermatitis
Dermatitis, or eczema, is a nonspecific term indicating inflammatory changes visible in the epidermal surface of the skin. No matter what the specific “subtype” of dermatitis, acute, subacute, and/or chronic changes may be seen. In acute dermatitis, changes consist of edema, papules, vesicles, serous discharge, crusting, scaling, and erythema. In subacute dermatitis, lesions are erythematous and scaly and may be edematous, but serous discharge and crusting are absent. In chronic dermatitis, changes consist of a scaly thickening of the skin, giving a washboard or tree bark appearance called lichenification. The phase, acute, subacute, or chronic, generally determines the prescribed treatment. Table 116.1 summarizes the features, treatment, and prognosis of several specific types of dermatitis. The different types of dermatitis are traditionally categorized based on associated manifestations, as with “atopic” dermatitis; mechanism, as with “contact” dermatitis; morphology, as with “nummular” dermatitis; and location, as with “hand” dermatitis. Dermatitis can be viewed as primarily caused by endogenous (e.g., atopy) or exogenous (e.g., external contact) factors, although both factors are eventually involved.
Atopic Dermatitis
Atopic dermatitis is considered an endogenous dermatitis. Affected patients will usually confirm the validity of the quote, “atopic dermatitis is the itch that rashes.” Patients typically have associated atopic diseases, such as allergic rhinitis or allergic asthma, and 70% give a family history of atopy. Atopic diseases are characterized by an imbalance in the normal T helper cell immune response, with TH2 cells infiltrating the affected tissues. This dominant TH2 response with a predominance of TH2-derived cytokines (e.g., interleukin-4, -5, and -13) over TH1 cytokines (e.g., interferon-γ and interleukin-12) is believed to play a key role in the pathogenesis of disease (1). Other immunologic alterations, including elevated serum immunoglobulin E (IgE) levels, a reduced delayed hypersensitivity response, decreased numbers of T-suppressor lymphocytes, increased percentage of B lymphocytes with surface-bound IgE-1, and decreased number or activity of natural killer lymphocytes, may be seen. However, not all patients with atopic dermatitis express these abnormalities, and their role in the development of atopic dermatitis is unclear.
Atopic dermatitis may be divided into subsets based on age of onset, infantile, with onset between 2 months and 2 years; childhood, with onset between 2 years and adolescence, and adult, with onset in adulthood. Areas of involvement are typically those that patients can scratch. Therefore, affected sites include the cheeks and extensor surface of the arms and legs in infants; the flexural surface of the arms, legs, neck, wrists, and ankles in children; and these same sites and often also (or only) the hands or face in adults. The morphology of the lesions varies based on duration and external trauma (e.g., rubbing and scratching). Acute lesions consist of erythema, edema, papules, vesicles, erosions, crusts, and scale, whereas chronic lesions consist of scaly papules coalescing into lichenified plaques, often with focal excoriations.
Treatment depends on the patient's age and the location of the dermatitis. For all ages, facial dermatitis is usually treated with over-the-counter (0.5% or 1%) hydrocortisone ointment or cream. In children, hydrocortisone or slightly more potent prescription steroids (e.g., hydrocortisone butyrate) are used on nonfacial sites. In teens and in adults, fluorinated mid-potency (e.g., triamcinolone acetonide, betamethasone valerate) to high-potency (e.g., fluocinonide, betamethasone dipropionate) corticosteroids are used on nonfacial sites. Care must be taken to avoid local and systemic side effects. Corticosteroids applied to large body surface areas may produce hypercortisolism and hypothalamic–pituitary–adrenal axis suppression in the same way that orally administered steroids may. Topical
P.1906
corticosteroids should always be used in combination with emollients, such as simple oil or water and oil moisturizing creams and lotions; see Chapter 113. Emollients protect, hydrate, and permit the skin to repair, thereby restoring the barrier between the body and the environment. Topical steroid use should be discontinued as soon as the lesions have cleared and should be restarted as needed. Not infrequently, patients with atopic dermatitis may require intermittent oral antibiotics for recurrent infection, or “dermatitis-triggering” colonization with Staphylococcus aureus.
|
TABLE 116.1 Summary of the Diagnostic, Therapeutic, and Prognostic Features of the Phases of Dermatitis |
|||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||
Alternative nonsteroidal anti-inflammatory agents, tacrolimus (Protopic ointment, 0.03% and 0.1%), which for many years has been used systemically to prevent organ transplant rejection, and pimecrolimus (Elidel cream) may be used if topical corticosteroids cannot be used or are ineffective. The U.S. Food and Drug Administration (FDA) has recommended their use “only as second-line agents for short term and intermittent treatment of atopic dermatitis in patients unresponsive or intolerant of other treatments.” This recommendation and “black-box” warning was prompted by animal studies and a small number of reports of cancer in patients treated with either of these topicals. Although it is known that systemic administration of tacrolimus may be associated with an increased risk of malignancy, especially lymphoma (pimecrolimus is not available for systemic use), any causative association with noncutaneous malignancies has been disputed by many because of the limited “case report evidence” as well as the fact that drug absorption with proper use is quite limited (2). On the other hand, concerns truly exist about local effects of these topicals, particularly in sun exposed sites, and include local immune suppression and alteration of normal deoxyribonucleic acid (DNA) repair capacity, possibly increasing the risk of infections and skin cancer (3). Until more data are available, use of these two topical agents should follow the recommendations of the FDA.
For patients unresponsive to these therapies, a consulting dermatologist would consider in-office phototherapy using ultraviolet (UV)-B radiation or photochemotherapy
P.1907
with psoralen and UV-A radiation (psoralen plus ultraviolet light of A wavelength [PUVA]). Because systemic corticosteroid therapy is associated with numerous long-term unacceptable side effects, it should be avoided in the treatment of atopic dermatitis. Alternative systemic immune modulating therapies, such as cyclosporine, interferon-γ, mycophenolate mofetil, and various immune modulating monoclonal antibodies, are still under investigation in the treatment of recalcitrant atopic dermatitis.
The generalist should be familiar with the nonpharmacologic measures to aid patients with atopic dermatitis. Measures that reduce anxiety, such as adjunctive massage therapy administered by the parents, may be helpful in children with atopic dermatitis (4). Also, although most patients with chronic atopic dermatitis have discovered which products to use and which to avoid, review of exacerbating factors may be helpful (e.g., irritating harsh soaps, recurrent wetting and drying, and coarse fabrics).
As a point of information, the generalist should inform patients with respiratory allergies that although desensitization immunotherapy may be helpful for allergic rhinitis and conjunctivitis, it will have no effect on the course of their atopic dermatitis. In contrast, addressing food allergies with appropriate dietary elimination is helpful in some children (5). Dietary modifications, especially in children, should be supervised by a qualified dietitian. Occasionally, adults may find certain foods exacerbate their dermatitis (e.g., gluten, milk). In these instances, as long as a balanced diet is maintained, a trial elimination of suspected triggers for 6 to 8 weeks should be encouraged. An occasional patient thought to have atopic dermatitis may instead have dermatitis herpetiformis. This is an extremely pruritic papulovesicular eruption on the extensor surfaces and lower back. Affected individuals have a gluten sensitivity with antigliadin antibodies or antiendomysial antibodies. The diagnosis is made by skin biopsy for routine histology and direct immunofluorescence; the latter will reveal IgA deposited in the dermal papillae.
Nummular Dermatitis
Nummular dermatitis is an idiopathic dermatosis seen most often in adults. Lesions consist of pruritic, sharply circumscribed, 1- to 2-cm, vesicular (acute) to lichenified (chronic), erythematous plaques favoring the extremities. Lesions may be mistaken for tinea corporis or impetigo because of their annular shape. Tinea is ruled out with a negative potassium hydroxide preparation (see Chapter 117), and impetigo is excluded based on the lack of honeycomb-like surface crust.
Treatment for nummular dermatitis is similar to that for atopic dermatitis. Emollients in combination with mid- to high-potency corticosteroids generally clear the lesions. To prevent recurrences after clearing, the topical corticosteroid should be tapered over 2 weeks with one application every other or every third day. Patients with unresponsive dermatitis may have misunderstood the importance of the topical steroid application or instead may have a secondary staphylococcal infection that requires specific treatment (Table 116.1).
Asteatotic Dermatitis
Asteatotic, xerotic, or dry skin dermatitis is most often seen in the wintertime in people living in low-humidity environments. Factors associated with decreased sebum oil production such as slowly declining testosterone levels in men and women after the sixth decade, cholesterol lowering medications, and any medications that reduce the production or effects of androgens (e.g., chemotherapeutic drugs and antiandrogens that suppress gonadal function or block androgen effects) may predispose patients to asteatotic dermatitis. Diminished epidermal and sebaceous gland sebum production allows loss of normally retained moisture in the stratum corneum. Skin changes typically begin with dryness in the early fall, which then progresses to patches of faint erythema appearing cracked or superficially fissured (Fig. 116.1, Color Plate section). Patients complain of a stinging, tight feeling to their skin with or without associated pruritus.
|
FIGURE 116.1. Asteatotic dermatitis (upper back and arm). Reticulate erythema highlighting minute cracks in the skin, diffuse dryness (asteatosis), and scale. (See color image.) |
Treatment involves hydration of the skin with warm baths or showers using oilated soaps (e.g., Oil of Olay Body Wash, Dove, Oilatum, or Aveeno Oilated Oatmeal Soap) followed by patting dry, leaving some moisture on the skin. A mid-potency corticosteroid ointment (as opposed to a cream) is then applied to the erythema, with a top coat of an emollient (see Chapter 113) to these and all areas of the skin. Extremely hot showers, which strip natural body oils; drying soaps; and stiff large-fiber clothing (e.g., wool) should be avoided. When the dermatitis has cleared, only the topical corticosteroid is discontinued; all other measures must be continued as long as the dry environmental exposure or sebum-reducing medication continues.
Contact Dermatitis
Contact dermatitis may be either irritant or allergic in nature. Irritant contact dermatitis may develop in anyone, whereas allergic contact dermatitis occurs only in people immunologically capable of recognizing and reacting to a particular allergen.
Irritant contact dermatitis to harsh chemicals results in a scalded, erythematous, moist appearance of the skin with peeling of the most superficial epidermis, leaving a lacy border. This is often caused by substances with extremes of pH, such as harsh alkaline cleansers and strong acid solutions. In contrast, mild irritants produce macular erythema that, with chronic exposure, may evolve into scaly plaques. With all forms of contact dermatitis, the eruption is limited to the area of contact. It is often the localized
P.1908
distribution and shape of the lesion that suggests the diagnosis, for example, irritant contact dermatitis at the forearm site of a solvent spill and allergic contact dermatitis on the earlobes bearing gold-colored earrings.
Allergic contact dermatitis (Fig. 116.2, Color Plate section) is caused by a delayed hypersensitivity reaction. Sensitization, if and when it develops, takes place through cutaneous exposure and requires approximately 1 week. A substance containing an allergen (hapten) is applied to the skin; the hapten binds to a protein to form a complete allergen, which is processed by the Langerhans cell, the resident antigen-presenting cell in the epidermis. As sensitization proceeds, the Langerhans cell moves into the dermis and through the lymphatics to the local lymph nodes, where it stimulates a lymphocyte clone that recognizes the antigen. If the substance is still in the skin 1 week after initial application or when subsequent re-exposure takes place, the Langerhans cells within the epidermis present the allergen to the memory T cells. These T cells secrete cytokines and other soluble mediators, which lead to recruitment of additional inflammatory cells (e.g., monocytes, neutrophils), resulting in the clinical picture of an acute dermatitis.
|
FIGURE 116.2. Acute contact dermatitis from shoes. (See color image.) |
The most common cause of allergic contact dermatitis is a plant dermatitis, caused by the Rhus genus, which includes poison ivy, oak, and sumac. In sensitized persons, a minute amount of the oleoresin (oil) from these plants will produce a vesiculobullous eruption in the areas of contact, beginning 6 to 72 hours after exposure. Patients often note that new blisters continue to develop over many days and assume that their scratching is causing the rash to “spread.” However, this is not the case; once the allergen is flushed from the skin, spreading cannot occur. The reason that new lesions may continue to develop for many days is because lesions take longer to evolve on skin that is thicker and penetration is slower (e.g., the palm) or where lesser amounts of oleoresin have contacted the skin. Also, continued unrecognized exposure to the oleoresin that may persist on clothing, tools, sports equipment, or the fur of pets may lead to “chronic poison ivy.” Allergens other than Rhus are less common sensitizers and typically produce a less pronounced dermatitis with erythema, edema, and mild or no vesiculation. Such allergens include nickel (commonly found in gold-colored costume jewelry); neomycin, benzocaine, and merthiolate in topical medicinals; fragrances and preservatives in cosmetics and personal products; and preservatives in ophthalmologic, otic, and dermatologic prescription and nonprescription medications. Various common occupational exposures may also cause allergic contact dermatitis. More common allergens include potassium dichromate in cement, dyes, or textiles; epoxy resins in adhesives, finishing products, and casings for electrical devices; natural rosin in adhesive materials; thiuram, mercaptobenzothiazole, and carbamates in rubber products; glyceryl monothioglycolate and paraphenylenediamine in hair wave and dye formulations; and acrylates in methylmethacrylate used in orthopedic surgery, dentistry, and nail sculpturing.
Allergic contact dermatitis characteristically develops unexpectedly, appearing “out of the blue” after months or years of unremarkable exposures. Evaluation for possible allergic contact dermatitis requires a detailed history of personal product use, occupational exposures, and avocational exposures followed by patch testing with standardized common and suspected allergens to confirm the diagnosis and identify the causative allergen. When the diagnosis appears to be allergic contact dermatitis but no direct exposure is uncovered, unrecognized exposures should be sought. For example, occasionally the allergen exposure occurs through contact with the “nonallergic” spouses’ personal products or work clothes.
The prevention of irritant and allergic contact dermatitis involves the recognition of irritants or allergens and elimination or minimization of exposure. Topical treatment is similar to that used for atopic dermatitis with emollients in combination with mid- to high-potency topical corticosteroids (Table 116.1). In cases of vesiculobullous dermatitis or dermatitis involving the face, hands, or genitalia, oral corticosteroids may be administered if no contraindications exist. Treatment should begin with 0.7 mg/kg/day of prednisone tapered over 2 weeks (e.g., 40 to 60 mg for 4 days, 30 to 40 mg for 5 days, and 20 mg for 5 days).
Contact Urticaria
Contact urticaria, although not a form of dermatitis, is a contact reaction. It may be caused by a histamine releasing nonimmunologic substance or an allergen-induced IgE-mediated immunologic reaction. The most common cause of immune mediated contact urticaria is latex protein (6,7). It is estimated that 10% of health care workers have been sensitized to natural rubber latex. Latex is ubiquitous in our environment, being present in over 40,000 medical and nonmedical devices and products. Childhood exposure to latex during surgical procedures greatly increases the risk for development of latex allergy. In fact, in one study of children who have experienced at least three surgical procedures, the prevalence of latex allergy was 34% (8).
Health care workers with latex contact urticaria typically present with a history of itching and hives in areas of contact with gloves. Identification of this allergy is important because, in addition to local reaction, latex exposure may cause generalized urticaria and even anaphylaxis, depending on how much histamine reaches the systemic circulation. Anaphylaxis is more likely to occur with oral, vaginal, rectal, or invasive intracorporeal latex contact. Diagnosis is made by in vitro latex IgE radioallergosorbent assay test (RAST) or in vivopatch, prick, or scratch testing. The former is preferred, because in vivo testing may cause anaphylaxis. However, RAST testing is not 100% sensitive; therefore, when allergy is strongly
P.1909
suspected and RAST testing is negative, referral to an allergist for skin testing is appropriate. Patients with latex allergy and all their health care providers must be educated about the potential life-threatening nature of this product and should be counseled on avoidance of all latex items, including latex gloves, balloons, condoms, and medical devices such as latex tubing, dental dams, surgeons’ gloves, and catheters. A Medic Alert bracelet should be worn and an epinephrine-containing autoinjector (Epi-Pen) should be prescribed and carried by the patient at all times for an emergency (see Chapter 30).
Hand Dermatitis
Hand dermatitis is a very broad term encompassing conditions that affect the hands exclusively, such as dyshidrotic hand dermatitis, also known as vesicular hand dermatitis, and several forms of dermatitis that may affect any area, including the hands (e.g., atopic hand dermatitis, nummular hand dermatitis, and contact hand dermatitis). Dyshidrotic or vesicular hand dermatitis is an idiopathic condition in which pinpoint to 2-mm vesicles develop on the sides of the fingers and often the palms. The lesions are intensely pruritic and usually cycle over 1 to 2 weeks, with cycles recurring at variable intervals every several weeks to several months. As each cycle resolves, there is focal desquamation (peeling) of the affected skin.
Hand dermatitis is idiopathic. Although this disorder is called dyshidrotic, there is actually no consistently identified abnormality in eccrine gland function (sweating). Similarly, the inflammation is not because of a contact allergy. However, because allergic contact dermatitis may occasionally mimic this condition (depending on mode of contact), any suspicion of allergic contact dermatitis should be investigated with patch testing. Treatment for vesicular hand dermatitis includes frequent emollient application and a high potency topical corticosteroid cream or ointment (e.g., fluocinonide) used for flares of disease. Followup visits should include examination for the steroid-induced side effect of skin atrophy (evidenced by shiny thin-appearing skin, loss of skin lines, or increased visibility of dermal vessels). Patients with recalcitrant dermatitis should be referred to a dermatologist for alternative therapies (e.g., phototherapy or photochemotherapy).
Infectious Eczematoid Dermatitis
Infectious eczematoid dermatitis is a secondary change within a primary form of dermatitis. Patients become infected with S. aureus and other organisms (usually gram-positive bacteria) and show extensive crusting and exudation within their primary dermatitis. Treatment includes systemic antistaphylococcal antibiotics. If methicillin resistant Staphylococcal aureus infection is suspected, bacterial culture and antibiotic sensitivity of the affected skin (swabbing the area) should be performed to direct the choice of antibiotic. Finally, treatment of the primary dermatitis should include soaks, topical corticosteroids, and emollients.
Intertriginous Dermatitis (Intertrigo)
Intertriginous dermatitis occurs in skin folds, such as the inframammary creases, abdominal folds, inguinal folds, gluteal cleft, finger and toe webs, and angles of the mouth. Patients develop moist erythema and, at times, fissures with weeping of serous fluid. Such skin changes provide a very hospitable environment for yeast and bacterial growth. The affected areas typically burn, sting, and itch.
The differential diagnosis of intertrigo includes primary Candida infection, seborrheic dermatitis, and psoriasis. Candida infection is diagnosed with a positive potassium hydroxide preparation (see Chapter 117) or, if unavailable, “swab” culturette submitted for fungal culture. Seborrheic dermatitis and psoriasis are usually diagnosed by identifying skin lesions elsewhere. When presumed intertrigo does not respond to therapy, unusual diagnoses such as Bowen disease (squamous cell carcinoma [SCC] in situ), extramammary Paget disease,Langerhans cell histiocytosis, and glucagonoma syndrome must be considered and a biopsy should be taken.
Therapy for intertrigo is directed at keeping the affected areas dry. Gauze may be placed in skin folds where appropriate, and a powder (e.g., Zeasorb or Zeasorb-AF, which contains an antifungal agent) or plain talc or baby powder should be applied frequently to dry the skin and reduce yeast colonization or infection. If obesity is the cause of the problem (e.g., abdominal or inguinal folds), weight reduction should be discussed with the patient (see Chapter 83). A cool environment is also beneficial. In edentulous patients with intertriginous dermatitis at the angles of the mouth because of overlapping skin, appropriate treatment for possible oral candidiasis and denture refitting should be prescribed. If these measures are ineffective, referral to a dermatologist for consideration of collagen injections may be considered. Collagen is injected into the crease formed by the opposing folds of skin. Although collagen injections must be repeated every 6 to 12 months, they may be a very worthwhile treatment for this chronic painful fissuring.
Seborrheic Dermatitis
Seborrheic dermatitis is a common condition present in approximately 3% to 5% of the population. Onset of seborrheic dermatitis is usually in early adulthood, and the course is characterized by frequent spontaneous remissions and exacerbations. In this disorder, an inflammatory epidermal hyperproliferation affects the areas the body more heavily populated with sebaceous glands, favoring the scalp and facial hair-bearing areas, central face
P.1910
(glabellar area and nasal folds), ears, presternal chest, axillae, umbilicus, inguinal folds, gluteal cleft, and perianal skin. Pruritus is variably present. Dandruff, a term commonly used synonymously with seborrheic dermatitis, is generally considered a noninflammatory (nonerythematous) scaling of the scalp skin.
Although the cause of seborrheic dermatitis is unknown, several observations have been made and hypotheses proposed over the years.Pityrosporum, a lipophilic yeast normally present on the skin, has been suggested as the cause of seborrheic dermatitis in that the yeast stimulates an immune response with resultant cutaneous inflammation. Although seborrheic dermatitis may occur in any individual, it occurs for unknown reasons with increased frequency and severity in patients with acquired immunodeficiency syndrome and Parkinson disease.
The treatment of seborrheic dermatitis is directed at decreasing epidermal hyperproliferation, inflammation, and Pityrosporum yeast using, respectively, topical tars, hydrocortisone, and ketoconazole. For the scalp, ketoconazole, selenium sulfide, zinc pyrithione, or tar shampoos and clear nongreasy mid- to high-potency corticosteroid solutions are preferred. Specifically, treatment for the scalp may include a medicated shampoo used every other night for 1 month, followed by prophylactic use once to twice weekly. If this alone is not effective, a fluorinated corticosteroid solution (e.g., Cormax Scalp Application, Lidex Solution) applied after shampooing should be added (two to three drops massaged into each quarter-sized of the affected scalp). Once under control, the corticosteroid is discontinued and repeated for recurrences only. For facial and body seborrheic dermatitis, hydrocortisone 1% cream (solution for the beard, mustache, eyebrows, outer auditory canal) may be used up to two times a day to control redness and scaling. Alternatively, ketoconazole cream (e.g., Nizoral 2% cream) may be used twice daily in a similar fashion. However, unlike hydrocortisone, ketoconazole cream may be continued after clearance to prevent recurrences.
Perioral Dermatitis
Perioral and sometimes periorificial dermatitis is an eruption of minute papules and pustules on a background of erythema and scant scale in a perioral or periorificial (mouth, eyes, and nares) location. Although it may occur at any age, it is most common in young women. It is uncommon and may be differentiated from acne by the lack of comedones and from contact dermatitis by the fact that it always spares the vermilion border, beginning 2 to 3 mm from the lip margin. Unlike allergic contact dermatitis, the most common symptoms are burning and stinging but not itching. Perioral/periorificial dermatitis, especially in the perinasal area, is a frequent precursor of acne in adolescent children and also frequently overlaps with perinasal seborrheic dermatitis and rosacea in adults.
The cause of perioral dermatitis is not known, but it has been associated with topical and aerosolized inhaled fluorinated corticosteroids and fluorinated toothpastes. Initial treatment is similar to that used for acne rosacea (see Chapter 115), but medications can usually be stopped in 4 to 8 weeks, often without a recurrence. If recurrences do occur, treatment is simply repeated.
Psoriasis
Definition and Prevalence
Psoriasis is an idiopathic benign epidermal hyperproliferation that affects 2% of the population (9,10). It is believed to be of multifactorial inheritance, with multiple genetic and environmental factors required for expression. Although the average age at onset of psoriasis is approximately 30 years, more than one third of patients develop the disease before age 20 years. Most patients who develop psoriasis have lifelong disease with periods of remission and exacerbation. Factors associated with exacerbation include sunlight/UV radiation deprivation (likely because of lack of beneficial UV radiation effects on psoriasis lesions but possibly also due to reduced serum levels of vitamin D), infections, certain drugs including lithium and antimalarials, local cutaneous trauma, alcohol ingestion, and physical and psychological stress.
Psoriasis may have a significant negative impact on many important aspects of life. Unlike other chronic diseases that may be easily concealed, psoriasis may be obvious because of thickened crumbly nails, heavy scalp scale, or hand, elbow, or knee involvement. The effect of the disease on the quality of life in patients with psoriasis has been compared with patients having other chronic diseases. When asked how many years of life patients would be willing to give up or how willing they would be to risk their lives to be free of their disease, patients with moderate psoriasis responded similarly to patients having had a kidney transplant. Patients with severe psoriasis responded similarly to those undergoing hospital-based dialysis (9). Patients with psoriasis involving exposed areas may also experience social rejection by people who believe that the disease is contagious or represents a manifestation of a disease or disorder they irrationally fear, such as acquired immunodeficiency syndrome (AIDS). Psoriasis may be a devastating financial burden also. It may cause physical and occupational disability, particularly when it affects the hands or feet or causes incapacitating psoriatic arthritis.
Clinical Presentation
Psoriasis may be divided into four major subtypes depending on the appearance of lesions, plaque, guttate, erythrodermic, or pustular.Chronic plaque psoriasis is the most
P.1911
common type of psoriasis. Patients exhibit one to many deeply erythematous, sharply demarcated, oval plaques several centimeters in diameter, with moderate to heavy silvery white surface scale, commonly on the scalp and over one or more extensor surfaces. Intertriginous plaques may also be present in the axillary, inframammary, umbilical, abdominal, inguinal, gluteal, and popliteal fossae. These fold area lesions have little or no scale and instead are moist and intensely erythematous. Patients who have numerous widespread plaques havegeneralized plaque psoriasis.
Guttate psoriasis is the next most common type of psoriasis. Approximately one third of patients have a sibling or parent with psoriasis (versus about 8% of the general population with such a family history) (11). Guttate psoriasis is characterized by an acute exanthem-like eruption of guttate (drop-like) erythematous, scaly papules, generally 1 mm to 1 cm in diameter. Although lesions are typically on the trunk and proximal extremities, the eruption may be widespread, involving the face, scalp, hands, and feet. Guttate psoriasis is often triggered by an infection, most often a streptococcal pharyngitis or a viral upper respiratory tract infection (URTI).
Erythrodermic psoriasis and pustular psoriasis are rare. In both types, a generalized exfoliative erythroderma (a scaly erythema) is present. In pustular psoriasis, crops of tiny, superficial, nonfollicular pustules develop, coalesce into “lakes of pus,” and then desquamate in waves of lacy scale. Erythrodermic and pustular psoriasis are severe diseases, particularly in patients with other chronic illnesses. Potential complications include high-output congestive heart failure, sepsis, intravascular volume depletion, and vitamin and nutrient deficiencies caused by increased requirements and losses.
Nail involvement is seen in 30% of patients. Although not pathognomonic, the most commonly noted changes are pitting (ice pick-like marks in the nail plate, Fig. 116.3), onycholysis (separation of the nail plate from the nail bed, with resultant white color caused by air between the plate and bed), and subungual hyperkeratosis (crumbly scale between the plate and bed). The latter may be very distressing because it is both obvious on casual observation and often difficult to adequately treat.
Extracutaneous Disease
Arthritis has been said to affect less than 5% to nearly one third of patients with psoriasis. Although it is generally believed that psoriasis and psoriatic arthritis are one disease involving two organ systems, it has been suggested that the two are separate entities occurring together by chance and that the activity of the psoriasis may modify or enhance the activity of simultaneously occurring joint disease (12). Regardless of cause, any patient with psoriasis and debilitating or destructive arthritis should be treated aggressively to prevent disease progression and disability.
|
FIGURE 116.3. Minute pits are commonly seen on the surface of nails in patients with psoriasis. |
Pathogenesis
Skin affected by psoriasis exhibits an accelerated rate of epidermal cell replication and a dysfunction of normal keratinocyte-to-keratinocyte inhibition of uncontrolled proliferation. Although not to the same degree, normal-appearing skin shows mildly accelerated proliferation. A basic issue that is still not fully understood is whether the primary defect triggering defective epidermal turnover resides in cytotoxic T cells, keratinocytes, locally produced cytokines, or other factors.
Treatment
Therapy for psoriasis depends on the degree of body surface area involvement and the clinical subtype of disease and prior response to therapy (10). One caveat should be noted by all clinicians prescribing any medications for patients with psoriasis, even mild psoriasis. Although systemic corticosteroids dramatically improve psoriasis acutely and in years past may have been used to treat psoriasis, systemic corticosteroids should be avoided. First, systemic corticosteroids would not be appropriate for psoriasis because it is a chronic disease requiring chronic therapy and, second, eventual corticosteroid withdrawal or dosage tapering may precipitate erythrodermic or pustular psoriasis.
Localized chronic plaque psoriasis is treated with bland emollients alone or combined with keratolytics (e.g., U-Lactin lotion, over the counter; AmLactin lotion, over the counter; Lac-Hydrin cream 12%, by prescription), topical corticosteroids, calcipotriene (Dovonex ointment or
P.1912
cream, a topical vitamin D derivative), or tazarotene (Tazorac 0.05% and 0.1% gel, a synthetic topical vitamin A derivative, nota bene, teratogen, Pregnancy Category X) applied twice daily. Although generic formulations of topical steroids tend to be relatively inexpensive, the vitamin D and vitamin A derivatives are very expensive. If these products made psoriasis vanish forever, patients would probably be happy to pay any price. But because this is not the case, patients who sacrifice to purchase them are likely to be disappointed. Topical steroids and vitamin D and vitamin A derivatives appear to be of similar efficacy in clinical trials; however, in a given patient one treatment may be much more effective than another. To achieve the best possible response, often some combination of a vitamin D or A topical and a corticosteroid is sought, requiring both a motivated patient and an empathetic clinician. A potential side effect of potent topical corticosteroids is atrophy (cigarette paper wrinkling or striae when severe). Side effects common to calcipotriene and vitamin A derivatives are irritation and stinging.
Generalized plaque psoriasis is difficult, time consuming, and expensive to treat with topical preparations. Also, the greater volume of topical corticosteroid needed to cover all the areas of psoriasis may ultimately produce effects similar to systemic corticosteroid administration. For these reasons, patients with generalized plaque psoriasis are frequently treated with phototherapy using broadband UVB radiation (UV radiation 290 to 320 nm wavelength; used since the 1920s), more recently introduced narrowband UVB (peak 311 nm wavelength; in contrast to broadband UVB, provides the optimal therapeutic wavlength), or photochemotherapy with the phototoxic agent 8-methoxypsoralen (Oxsoralen Ultra) orally in combination with controlled UVA radiation (UV radiation 320 to 400 nm wavelength) given in a PUVA. Patients are generally treated three times a week until clearance occurs and then may receive maintenance light treatments (PUVA only; UVB maintenance should not be used because of the risk of sunburn) or may discontinue treatments until the next flare of psoriasis occurs. A patient should never be given 8-methoxypsoralen to be used with natural sunlight or in a suntan parlor because severe burns and even death may occur. Also, self-administered light treatment even without a phototoxic agent is best avoided because careful monitoring is difficult and severe burning may result. Over a long period, PUVA therapy increases a patient's risk of skin cancer, both nonmelanoma and likely also melanoma skin cancer. Therefore, patients treated with PUVA should be followed throughout their lives, preferably with yearly full skin examinations. Alternative therapies to phototherapy and photochemotherapy include methotrexate, acitretin, cyclosporine (12,13), and “the biologics.”
Guttate psoriasis, particularly with the initial episode, is usually very responsive to most treatments. Sunlight or in-office UVB phototherapy combined with emollients and low-potency topical corticosteroids often work well. Additionally, because triggering infections, especially streptococcal pharyngitis, may precipitate guttate psoriasis, appropriate evaluation should be performed.
Erythrodermic and pustular psoriasis may cause severe and even life-threatening illness, particularly in elderly patients with cardiovascular disease. Depending on the severity of the psoriasis and underlying medical problems, patients may require hospitalization, warm baths, bland emollients, and systemic therapy with acitretin (a synthetic retinoid), weekly low-dose methotrexate, or cyclosporine. Patients without infection may have signs and symptoms identical to those seen with sepsis, with cyclic fevers up to 104°F (40°C) and an increase in white blood cell count up to 40,000 cells per cubic millimeter with neutrophilia, tachycardia, and orthostatic hypotension, so that possible sepsis must be excluded with blood and urine cultures and other appropriate testing. The hemodynamic instability seen is caused by marked vasodilation and increased cardiac output and is particularly problematic in the setting of pre-existent cardiovascular disease or volume depletion. In addition, vitamin and nutrient deficiencies may result from the accelerated epidermal turnover rate. After all the acute cutaneous and systemic problems have been addressed and the patient's cutaneous disease is controlled, the systemic therapy for psoriasis generally must be continued or PUVA substituted to prevent severe flares.
Patients requiring systemic therapies for psoriasis are probably best cared for with the consultation of a dermatologist. Those receiving methotrexate, acitretin, or cyclosporine must be monitored closely. Methotrexate and cyclosporine yield comparable response rates in most types of moderate to severe psoriasis (12), whereas acitretin is extremely useful in treatment of pustular psoriasis. Methotrexate is an abortifacient and must not be taken by either men or women within 3 months of planned conception. The most important side effects of methotrexate are acute cytopenias and chronic hepatitis and cirrhosis. Acitretin is teratogenic. Women taking acitretin must abstain from alcohol and wait 2 years after drug cessation to begin to try to conceive. For this reason, it may be best to avoid this medication totally in women of child-bearing potential. Important potential side effects of acitretin include hypertriglyceridemia and hypercholesterolemia, hepatitis, pseudotumor cerebri, bony hyperostosis, hair loss, fragile skin, painful palmar and plantar desquamation, and arthralgias. Cyclosporine has many notable side effects, including hypertension, decreased renal blood flow, glomerular and tubular toxicity, paresthesias, and anergy (13). Whether cyclosporine is associated with an increased risk of cutaneous or lymphoproliferative malignancies in nontransplant patients is unclear (14).
The most recently introduced systemic therapies for psoriasis are the “biologics.” These agents are targeted at
P.1913
the immunologic alterations found in psoriasis. Like all systemic therapies, they are reserved for moderate to severe psoriasis. As they have not been in clinical use for 20 or 30 years, potential long-term side effects are not known, something both clinicians and patients must understand and accept prior to going forth with therapy. The FDA has approved three parenteral agents for treatment of moderate to severe psoriasis, alefacept (LFA3TIP) and efalizumab (anti CD11a) are both inhibitors of T-cell activation while etanercept is an inhibitor of tumor necrosis factor-α (TNF-α). These agents have been shown to be more effective than placebo in studies of 3 months or longer. Etanercept has also been FDA-approved for the treatment of psoriatic arthritis. In the short term, these agents appear relatively safe; alefacept requires monitoring of T-lymphocyte counts, efalizumab requires monitoring of platelet counts, while etanercept therapy should include baseline tuberculin skin testing and observation during therapy for signs or symptoms of infection, lupus-like syndromes, neurologic events (especially new onset of demyelinating disease), and heart failure. In general, etanercept should not be used in persons with demyelinating diseases or congestive heart failure (15).
Although these medications are generally well tolerated during therapy, the greatest concern is the unknown long term risk for malignancy and lymphoproliferative disorders. Note should be made that a recent study in patients with rheumatoid arthritis treated with TNF-α inhibitors, compared with those patients not so treated, followed for less than 4 years found a relative risk of 4.9 for the development of lymphoma (16). One other factor regarding the biologics is their cost. Regardless of “who” is paying for them, ultimately the expense may impact individual patients in the form of higher insurance rates or even difficulty in getting insurance given their diagnosis of psoriasis. It has been estimated that although the cost of 3 months of treatment with one of the biologics is $16,000 and upward, given response rates of less than 50%, “successful treatment” is $35,000 and upward (17,18). It should also be realized that most patients on one of the biologics receive more than 3 months of biologic therapy per year. These costs compare with similar estimates of “successful treatment” costs (taking into consideration expected response rates for other therapies) of other therapies, including, methotrexate—$5,400; cyclosporine—$14,200; acitretin—$17,300; PUVA—$5,700; and UVB—$5,100 (17). It seems clear that the biologics are a wonderful addition to the therapeutic armamentarium for psoriasis, especially in patients with severe disease who have exhausted other possible therapies, however, as should be said about innumerable medications, thoughtful consideration of options, long-term toxicities, and implications of biologic therapy should be undertaken before initiating therapy.
Other investigational therapies may eventually prove useful. Among these are thiazolidinediones (e.g., pioglitazone), particularly attractive for patients also requiring oral hypoglycemic agents. Thiazolidinediones are insulin sensitizing agents that act as ligands for the peroxisome proliferator-activated receptor-γ, a member of the nuclear hormone receptor superfamily that includes the retinoic acid receptor and the vitamin D receptor (notably, both these receptors are targets of presently available FDA-approved topical and systemic psoriasis therapies). The potential beneficial effect is believed to occur through inhibition of cell proliferation and promotion of cell differentiation (19,20). Although the data are limited, a 10-week, double-blind, randomized, placebo-controlled, parallel group study of 70 nondiabetic patients with moderate to severe psoriasis treated with 15 mg, 30 mg, or placebo showed clearing or near clearing of psoriasis in 40% of treated patients compared with 12.5% of patients receiving placebo (21). Hopefully, additional studies will reveal whether thiazolidinediones will be useful in the treatment of psoriasis. Finally, the possible role of gluten sensitivity in psoriasis and psoriatic arthritis has yet to fully elucidated. Notably, it has been reported that patients having elevated serum gliadin antibodies see improvement in their psoriasis with the institution of a gluten-free diet (22, 23, 24).
Specific References*
For annotated General References and resources related to this chapter, visit http://www.hopkinsbayview.org/PAMreferences.
P.1914