CHAPTER 43 SKIN DISORDERS
Practice of Geriatrics
CHAPTER 43 SKIN DISORDERS
Randy Berger, M.D., and Barbara A. Gilchrest, M.D.
Pathophysiology: Age-Associated Changes in Normal Skin
Diseases—Diagnosis and Management
Skin is the interface between people and their environment that protects the other organs of the body from excessive temperature changes, mechanical injury, ultraviolet irradiation, toxic chemicals, and microbial pathogens. It is also a tactile organ through which individuals receive pleasurable stimuli and assess their physical surroundings. With age, the skin performs each of these vital functions less well. Skin is also readily visible and hence of great psychological and social as well as physiologic importance. For these reasons, the morphologic changes that accompany aging in the skin often affect an individual as much as the functional changes.
Dermatologic problems are exceedingly common, especially among the elderly, and are frequently among the chief complaints that bring geriatric patients to the physician. It has been estimated that 6% of all physician visits are prompted by disorders of the skin.1 Moreover, examination of more than 20,000 noninstitutionalized Americans revealed that 40% of those over the age of 65 suffered from a dermatologic disease sufficiently severe, in the opinion of the consulting dermatologist, to justify at least one physician visit, and that the average affected individual had 1.5 such disorders.2 These figures do not include the nearly universal “cosmetic” changes characteristic of aging skin, which may lower self-esteem and may have a measurable negative impact on society’s perception of the elderly.3
Morphologic and probably even physiologic age-associated cutaneous changes are most pronounced in fair-skinned individuals, in whom sun damage is superimposed on intrinsic aging. The major stigmata of aging in the skin—wrinkling, “dryness” (roughness), uneven pigmentation, and cancer—are indeed virtually restricted to habitually sun-exposed areas. However, these sun-induced changes, which have dominated the public and even medical perception of cutaneous aging, are only one aspect of a subtle but undoubtedly biologically significant process that gradually alters the function of normal skin and its response to a large number of disease states. The following sections review the age-associated changes now recognized in normal skin and discuss selected disorders of the skin with special relevance to the elderly.
PATHOPHYSIOLOGY: AGE-ASSOCIATED CHANGES IN NORMAL SKIN
Histologic features associated with aging in human skin are shown schematically in Figure 43-1. The most striking and consistent change is flattening of the dermoepidermal junction, with effacement of both the dermal papillae and the epidermal rete pegs. Ultrastructurally, there is also a decrease in villous cytoplasmic projections of the epidermal basal cells into the dermis.4,5 This results in a considerably smaller contiguous surface between the two compartments, presumably less “communication” and nutrient transfer, and less resistance to shearing forces. Loss of dermal thickness approaches 20% in elderly individuals and may account for the paper-thin, sometimes nearly transparent quality of their skin. The remaining dermis is relatively acellular and avascular. Precise histologic concomitants of wrinkling, if any, are unknown, although age-related loss of normal collagen and elastin fibers is probably a contributory factor. Table 43-1 lists the major functions of the skin that decline with age.4 Many of these functions are necessarily interrelated or overlapping.
Figure 43-1 Histologic changes in aging normal skin. Schematic drawings emphasize the age-associated flattening of the dermoepidermal junction (basement membrane zone [BMZ]): loss of dermal and subcutaneous mass; shortened capillary loops; and reduced numbers of melanocytes, Langerhans’ cells, and mast cells. Note that the average thickness of the stratum corneum (barrier layer) and viable epidermis (area above BMZ) does not vary with age. In most body areas, epidermal thickness is approximately 0.1 mm; dermal thicknesses range from 1.0 to 4.0 mm, depending on body site. Melanocyte densities range from 1000/mm2 to 2000/mm2 surface area in most body areas; Langerhans’ cell density is approximately 500/mm2. (From Gilchrest BA: Age-associated changes in the skin. J Am Geriatr Soc 30:139–143, 1982.)
TABLE 43-1 PHYSIOLOGIC PARAMETERS IN HUMAN SKIN THAT DECLINE WITH AGE
An age-associated decrease in epidermal turnover rate of approximately 30% to 50% between the third and eighth decades has been determined by a study of desquamation rates for corneocytes (cells of the stratum corneum) at selected body sites; other investigators have reported a corresponding 100% prolongation of the stratum corneum replacement rate in old men as opposed to young men. The repair rate in injured skin likewise declines with age.6 In vitro studies of cultured keratinocytes and fibroblasts demonstrate a diminished responsiveness to mitogens and an enhanced sensitivity to growth inhibitors in adult compared with newborn cells. These findings are even more marked in cells from older adults.7,8 and 9 In general, as cells age, they become less responsive to signals in their environment. Linear growth rates of hair and nails also decrease by approximately 30% to 50% between early and late adulthood.
Although stratum corneum thickness and degree of compaction remain constant, an age-related decrease in surface barrier function, as measured by percutaneous absorption of at least some substances, has been reported. This increased absorption is accompanied by a decreased dermal clearance rate for the materials, possibly increasing the risk of an irritant or allergic contact dermatitis.10
Decreased sensory perception has been documented in elderly skin using the techniques of optimal stimulus in grams for light touch, vibratory sensation, and corneal sensation. Pacinian and Meissner’s corpuscles, the cutaneous end-organs responsible for pressure perception and light touch, progressively decrease to approximately one-third their initial average density between the second and ninth decades of life.11
Early studies demonstrated that eccrine sweating is markedly impaired with age. Spontaneous sweating in response to dry heat, measured on digital pads, is reduced by more than 70% in healthy elderly subjects compared with young control subjects. The response is attributable primarily to a decreased output per gland, although the number of eccrine glands also decreases by approximately 15% during adulthood in most body sites.11
Decreased vascular responsiveness in the normal skin of old versus younger individuals has been documented by measuring vasodilation and transudation after application of standardized chemical irritants and exposure to a standardized ultraviolet dose. The decreased erythematous response is probably in part attributable to the striking age-associated loss of dermal venules, although decreased responsiveness of individual vessels may also be responsible. Compromised thermoregulation, which predisposes the elderly to hypothermia and possibly to heat stroke, may be due in part to reduced vasoconstriction or vasodilation of dermal arterioles, in part to decreased eccrine sweat production, and in part to loss of subcutaneous fat, all of which occur with advancing age.4
Dermoepidermal separation has been reported to occur more readily in the elderly under experimental conditions, as might be anticipated from the histologic finding of reduced interdigitation between the dermis and the epidermis. The poor adhesion between these two cutaneous compartments undoubtedly explains the propensity of elderly people to show “torn” skin and superficial abrasions following minor trauma, such as removal of bandages, and to form bullae in edematous sites. It may also contribute to the increased prevalence of certain bullous dermatoses in the elderly.11
An age-associated decrease in delayed hypersensitivity reactions in human skin is manifested by a relative inability of healthy older subjects to develop sensitivity to dinitrochlorobenzene. Similarly, elderly subjects have a lower rate of positivity for standard test antigens compared with young adult controls. This decrease undoubtedly partly reflects the well-documented loss of circulating thymus-derived lymphocytes and their decreased responsiveness to standard mitogens. Additionally, with age there is decreased elaboration of interleukin-1, interleukin-2, and other cytokines.12 Also implicated is the nearly 50% reduction in morphologically identifiable epidermal Langerhans’ cells (the cell population believed to be responsible for immunosurveillance in the skin) that occurs between early and late adulthood. The further loss of Langerhans’ cells in skin habitually exposed to the sun is postulated to predispose it to skin cancer.
Cutaneous manifestations of immediate hypersensitivity also decrease with age. In one well-controlled epidemiologic study of over 3000 subjects, the percentage of people with at least one positive wheal-and-flare reaction to a standard battery of potential allergens fell from 52% at age 20 years to 16% at age 75 years. Smaller groups of subjects with at least 3, 7, or 11 positive test results showed parallel reductions with advancing age. Investigators were unable to determine the relative contributions of systemic versus local cutaneous changes in this decline.13 Another study demonstrated an approximately 50% reduction in mast cells (the source of histamine in the skin) in the papillary dermis of buttock skin in old adults; this was associated with a corresponding reduction in stimulated histamine release.
A decrease in sebum production of approximately 60% accompanies advancing age in both men and women. This has been attributed to the concomitant decrease in production of gonadal or adrenal androgens, to which sebaceous glands are exquisitely sensitive. The clinical effects of decreased sebum production, if any, are unknown. There is no direct relationship to xerosis or seborrheic dermatitis.
One endocrine function of human skin that is thought to decline with age is vitamin D production. In response to sun exposure, the epidermis converts 7-dehydrocholesterol to previtamin D, which is further metabolized and ultimately hydroxylated in the liver and kidneys to the active form responsible for regulation of calcium homeostasis. Between early and late adulthood, the level of epidermal 7-dehydrocholesterol decreases by approximately 75%, suggesting that the lack of an immediate precursor may limit vitamin D production in the elderly.14 These concerns are reinforced by studies that have shown occult osteomalacia (bone loss due to vitamin D deficiency) as determined by bone biopsy in 20% to 30% of women and in up to 40% of men presenting with hip fractures; other laboratory evidence of vitamin D deficiency or secondary hyperparathyroidism has been found in 48% of homebound elderly.15 It is thus postulated that in elderly individuals already compromised by osteoporosis, reduced vitamin D synthetic capacity, compounded by insufficient sun exposure, sunscreen use,16 or poor dietary intake of vitamin D, may cause osteomalacia and hence further increase the risk of trabecular bone fracture.
When evaluating a patient for a dermatologic complaint, it is essential to take a complete medical history, paying particular attention to the medications being taken. It is important to inquire what topical treatments, either prescribed or self-determined, the patient is employing. Over-the-counter topical anesthetics, cosmetics, or isopropyl alcohol, for example, can each exacerbate various skin conditions. Bathing habits and exposures to harsh detergents and other irritants should be discussed. The duration of a complaint, response to various treatments, and the presence of close contacts with a similar condition can suggest diagnostic possibilities.
Ideally, the entire cutaneous surface should be examined with adequate lighting. Often physical findings in areas other than those mentioned by the patient can give clues to the diagnosis. For example, genital lesions, about which the patient may not necessarily complain, can help make a diagnosis of scabies. A full skin examination also allows detection of cutaneous malignancies or other significant conditions of which the patient may not be aware. Finally, as mentioned earlier, owing to blunted vascular and immune responses, the skin findings may be more subtle in elderly patients than in younger ones with similar disorders, which often makes diagnosis more challenging in this population.
DISEASES—DIAGNOSIS AND MANAGEMENT
The following discussion expands on the diagnosis and management of selected topics in dermatology. Most of the disorders included are particularly prevalent in the geriatric population, and a familiarity with them will aid in their recognition when caring for such patients. Pruritus and xerosis are among the most frequent dermatologic complaints of the elderly. Seborrheic dermatitis, while less troublesome symptomatically, is commonly seen among geriatric patients and may be associated with concomitant disorders in this population. The elderly are particularly likely to be taking a multiplicity of medications, putting them at risk for adverse drug reactions. When caring for such patients, it is important to recognize both the more common and less severe drug eruptions as well as the uncommon, life-threatening ones. Bullous pemphigoid, while not particularly common in the general population, is seen with significantly higher frequency in the geriatric population and is presented here as a prototype of autoimmune bullous disease.
Infections of all types are common in the elderly, and two infections involving the skin are discussed in this chapter. Herpes zoster is a frequent viral infection of the skin that rises in incidence with increasing age. It is responsible for significant morbidity in some patients. Scabies, while not restricted to the elderly, is often more challenging to diagnose in geriatric patients and, if overlooked, can lead to marked discomfort and widespread infestation among nursing home residents and health care workers. Finally, skin cancer is an important dermatologic condition that especially affects the elderly owing to their many years of ultraviolet irradiation. Early diagnosis and treatment can significantly affect morbidity and mortality in this population.
Elderly people often experience localized or generalized pruritus. For some it is a minor annoyance; for others it leads to extensive, slow-healing excoriations or loss of sleep with associated irritability and impaired mental function.
Many patients presenting to the physician because of pruritus in fact have an eruption that is responsible for the symptom,17 although its other manifestations may be so subtle that the patient or even the physician does not notice the rash. Because inflammatory responses may be muted in the elderly, a careful history and physical examination are necessary before primary disorders of the skin such as eczema, early bullous pemphigoid, urticaria, scabies, or pediculosis are excluded. Proper identification of a causative dermatosis leads to effective treatment in most patients and allows the patient to avoid the hematologic, radiographic, and other laboratory procedures that constitute the work-up for unexplained generalized pruritus.
Table 43-2 lists the most common systemic disorders associated with generalized pruritus. Among all patients seeking medical attention for pruritus, the prevalence of underlying systemic disease has been reported as 10% to 50%,18 the percentage depending on patient selection, diagnostic evaluation, and period of follow-up. Numerically, perhaps the most important known cause of persistent generalized pruritus is chronic renal failure. However, the degree of renal failure necessary to cause pruritus is unknown, complicating interpretation of this symptom in the elderly patient with mild to moderate renal insufficiency. From a practical viewpoint, it is probably unwise to attribute pruritus to otherwise asymptomatic renal failure or to renal insufficiency not requiring specific therapy for metabolic imbalance.
TABLE 43-2 SYSTEMIC DISORDERS SOMETIMES ASSOCIATED WITH PRURITUS IN THE ELDERLY
Pruritus is probably the most distressing and consistent symptom of chronic cholestasis, which underlies all the hepatic disorders listed in Table 43-2. Overall, pruritus occurs in approximately 20% to 25% of jaundiced patients, but it is rare in those with hepatic disease lacking cholestasis. Drugs that can cause pruritus by inducing cholestasis include phenothiazines, tolbutamide, erythromycin estolate, anabolic hormones, estrogens, and progestins.19 Other drugs that can result in considerable pruritus without cholestasis are opiates.
Approximately 30% to 50% of patients with polycythemia vera and up to 20% of patients with Hodgkin’s disease experience pruritus.18 The incidence and significance of pruritus in other lymphomas and leukemias are unknown, but the occasional association cannot be disputed. Generalized pruritus has been reported as an initial symptom in patients with multiple myeloma, Waldenström’s macroglobulinemia, and benign gammopathies. Iron deficiency anemia has been reported as the cause of generalized pruritus in more than 50 patients,20 including six with polycythemia,21 although this association is apparently rare. Pruritus attributable to endocrine or specific “miscellaneous” causes is rare, and many elderly people experience generalized pruritus for which there is no apparent explanation. Hence, one must either accept a higher incidence of idiopathic pruritus with advancing age or infer the existence of “senile pruritus.” Physiologic factors that may contribute to this hypothetical entity include age-associated alterations in the skin, peripheral nerve endings, and dermal neuropeptide release. Alterations in the barrier function of the skin, which possibly facilitate low-grade irritant dermatitis, include decreased keratohyalin granule formation in the epidermis, decreased skin surface hydration,22 diminished stratum corneum lipids, and a slower rate of stratum corneum barrier repair.23 In addition, altered sensory thresholds of C-fiber neurons as well as modifications in the synthesis, release, and clearance of dermal neuropeptides, such as substance P, histamine, neurokinin A, calcitonin gene-related peptide, and other mediators with opiate activity,24 may also play a role.
The appropriate laboratory evaluation for the patient with unexplained generalized pruritus remains a matter of opinion because cost-benefit ratios for individual procedures have not been determined. Measurement of serum creatinine, blood urea nitrogen, bilirubin, and hepatic enzymes with a complete blood count and urinalysis seem to constitute a reasonable survey; a chest radiograph may also be justified as a screening test for malignancy. Physical examination should include examination of the lymph nodes, liver, and spleen. Additional tests may be suggested by the history, review of systems, or physical examination.
The pathophysiology of pruritus associated with systemic disease is incompletely understood, and the optimal therapy is the same as that for the underlying disease whenever possible. Specific approaches to the treatment of the pruritus itself are available in a few instances, but for most patients nonspecific therapies must be employed.25 Often it is worthwhile to prescribe an emollient, even in the absence of clinical xerosis, because minimal or intermittent “dryness,” present in virtually all elderly individuals, may notably exacerbate pruritus of another cause. Patients should be cautioned specifically against topical application of alcohol or hot water (both of which may temporarily relieve but ultimately exacerbate pruritus) or excessive washing, especially with soap. Topical application of menthol and camphor in an emollient base, such as in Sarna lotion, may provide considerable temporary relief; other topical anesthetics can be used only at the risk of allergic sensitization. Oral antihistamines are widely prescribed for pruritus of all causes, although their efficacy is slight in most instances, even when combinations of H1 and H2 blockers are used. The use of antihistamines by the elderly may result in additional problems of urinary retention, paradoxical restlessness, or significantly impaired psychomotor function. Newer nonsedating antihistamines pose fewer problems in terms of neurologic side effects; however, care must be taken to avoid potential drug interactions.
Xerosis is the term used to describe the “dry” or rough quality of skin that is almost universal among the elderly. The condition may be generalized but is especially prominent on the lower legs and is exacerbated by the low-humidity environments classically found in overheated rooms during cold weather. The term xerosis is a misnomer; the initial assumption that the disorder results from a lack of water in the skin overall has been disproved.26 In vivo and in vitro measurements demonstrate diminished hydration of the superficial portion of the stratum corneum, but the deeper portion maintains normal hydration.27 The occasional classification of xerosis as a disorder of the sebaceous (oil) glands is similarly without experimental basis.2 Xerosis probably reflects minor abnormalities in epidermal maturation that in turn result in an irregular surface of the stratum corneum.24 Xerotic skin in the elderly is often pruritic and may show evidence of inflammation, probably due to defects in the stratum corneum, with secondary entry of irritating substances into the dermis. The resulting condition, called erythema craquelé or winter eczema, responds promptly to topical corticosteroid ointment or emollients, although these preparations do not correct the xerosis itself.
Frequent, regular use of a topical emollient makes dry skin more attractive and more comfortable and prevents the complications discussed previously. Emollients are most effective when applied to already moistened skin (e.g., immediately after the bath or shower). “Heavy,” frankly greasy emollients have the additional property of perceptibly coating the skin, producing a smooth surface film, and they are usually better barriers against evaporation than are more cosmetically elegant preparations. Preparations containing ammonium lactate28 or other alphahydroxy acids are especially effective in restoring skin barrier function and improving xerosis. Finally, it should be noted that emollients applied to the skin immediately after bathing retain water more effectively than gels or oils added to the bath water that coat the bathtub as well as the skin, producing a dangerously slippery surface that is difficult to clean.
Seborrheic dermatitis is a common dermatologic condition in the geriatric population.29,30 and 31 Clinically, it presents as erythema and greasy-appearing scales in what is referred to as a seborrheic distribution, namely, the scalp, ears, central face (particularly the eyebrows, glabella, perinasal area, nasolabial folds, and beard area), and the central chest and interscapular areas. When present in the scalp, it is referred to in lay terms as dandruff. Seborrheic dermatitis is found with greater frequency among patients with underlying neurologic conditions, such as Parkinson’s disease, facial nerve injury, spinal cord injury, poliomyelitis, and syringomyelia, as well as in patients taking neuroleptic medications with parkinsonian side effects. Human immunodeficiency virus (HIV) infection has also been associated with severe seborrheic dermatitis.
The role of resident lipophilic yeast, Pityrosporum ovale, is controversial, although studies have shown that the organism is present in greater number in patients with seborrheic dermatitis. Treatment is directed at either killing the pityrosporum yeast with antifungal preparations, such as ketoconazole cream, or directly suppressing inflammation by means of low-potency topical steroids. It should be noted that topical ketoconazole also has some anti-inflammatory properties. In a double-blinded study comparing 2% ketoconazole cream with 1% hydrocortisone cream, a therapeutic response was noted in 80.5% of subjects using ketoconazole and 94.4% of those using hydrocortisone, demonstrating a somewhat higher efficacy of hydrocortisone, although establishing ketoconazole as an effective, steroid-sparing alternative.32 For hair-bearing regions, shampoos containing ketoconazole, selenium sulfide, salicylic acid, zinc pyrithione, or tar are effective.
Adverse cutaneous reactions to medication include expected, usually dose-related, side effects such as acneiform eruptions following corticosteroid administration or xerosis following retinoids, and unexpected, immune-mediated, allergic reactions. These latter reactions typically occur within 3 days to 2 weeks of challenge and persist for up to 2 weeks after the drug has been discontinued. Rechallenge results in a more rapid onset of the eruption. Less commonly, a patient may have an adverse reaction to a medication after weeks, months, or, rarely, years of use. Although any medication can cause a drug eruption, certain medications are statistically more likely to do so. In two studies surveying separately over 22,000 and 15,000 inpatients, the Boston Collaborative Drug Surveillance Program identified the following drugs as having the highest incidences of drug eruption: amoxicillin, ampicillin, penicillin, semisynthetic penicillins, trimethoprim-sulfamethoxazole, transfused blood, cephalosporins, gentamicin sulfate, acetylcysteine, allopurinol, quinidine, and dipyrone. Conversely, digoxin, antacids, meperidine, promethazine, and acetaminophen were among the medications administered to more than 1000 patients with no reported cutaneous eruptions.33,34
Central to management of a drug eruption is discontinuation of the culprit medication. This is particularly essential in patients with the more serious and potentially life-threatening reactions. Midpotency topical steroids, antihistamines, and antipruritic lotions provide symptomatic relief.
The most common form of drug eruption is the morbilliform or exanthemous eruption, sometimes referred to as a maculopapular eruption. It is characterized by discrete and coalescing erythematous macules and papules symmetrically distributed on the trunk and extremities. The most common causative agents are those listed in the previous paragraph. Morbilliform eruptions typically begin within 1 week of exposure, except in the case of penicillins, which may cause eruptions beginning 2 weeks or longer after the initial exposure.35
Other forms of drug eruption include photosensitivity, as is seen with doxycycline or thiazides; a lichenoid or lichen planus-like eruption, seen with gold and phenothiazines; and urticaria, often associated with penicillin or iodine-containing contrast media. A fixed drug eruption is manifest by one or few, red to violaceous, round plaques that recur in the same location if the patient is rechallenged. These lesions resolve with hyperpigmentation, which becomes more pronounced with each episode. Drugs that cause a fixed drug eruption include tetracyclines and nonsteroidal anti-inflammatory drugs.36 Vasculitis, presenting as palpable purpura, can occur as the result of a hypersensitivity reaction to a medication, among many other possible causes. Immune complex formation can lead to a serum sickness reaction, characterized by an urticarial eruption, fever, arthritis, nephritis, and sometimes neurologic symptoms. Penicillins, sulfonamides, and streptomycin are among the causative agents.35
Some of the less common reactions are important because of their life-threatening nature. These include hypersensitivity reactions, anaphylaxis, exfoliative erythroderma, erythema multiforme major (Stevens-Johnson syndrome), and toxic epidermal necrolysis (TEN). These conditions often require hospitalization with intensive supportive care as well as discontinuation of the causative agent. Hypersensitivity reaction was first described with phenytoin and is now recognized with drugs other than anticonvulsants, particularly sulfonamides. It is a multisystemic response manifested by a cutaneous eruption, which may be of any type, in conjunction with fever, adenopathy, hematologic abnormalities, and hepatitis.37 It should be noted that phenytoin, carbamazepine, and phenobarbital cross react with each other, and all three agents are contraindicated in patients sensitive to any of them. Anaphylaxis occurs in a spectrum of IgE-dependent reactions including urticaria, bron-chospasm, laryngeal edema, and hypotension. Penicillins are the most common drugs associated with anaphylaxis, and the reaction is more likely to occur with intravenous administration.35 Exfoliative erythroderma presents as diffuse erythema and scaling. Temperature, fluids, electrolytes, and nutrition must be carefully monitored. Erythema multiforme is recognized by the presence of pathognomonic target lesions with an erythematous periphery and a dusky center, which sometimes progress to a central blister or erosion. When the mucous membranes are involved the eruption is classified as the Stevens-Johnson syndrome. When large areas of skin are sloughed it is termed toxic epidermal necrolysis. TEN is characterized by skin tenderness and a positive Nikolsky’s sign, along with shearing off of the epidermis with lateral force, which may appear de novo or may evolve from severe erythema multiforme. Again, fluid and electrolyte management and the avoidance of sepsis are crucial. The mortality rate for TEN is 30% to 50%, and patients are best managed in a burn unit.38
Bullous pemphigoid (BP) is an idiopathic, antibody-mediated disease, which can be differentiated clinically, histologically, and immunologically from the much less common pemphigus vulgaris. The elderly are affected most commonly, and, conversely, BP is the most common immune-mediated blistering disease affecting older patients. Untreated, this disease varies in severity from mild to disabling, and the prolonged loss of an effective cutaneous barrier may be fatal. The disease is self-limited, lasting months to years, but recurrences follow disease-free periods in a minority of patients.39
Bullous pemphigoid is characterized clinically by tense bullae arising on either erythematous or normal-appearing skin (Fig. 43-2). Preceding or accompanying pruritus is common and may be intense. Crusted erosions and urticarial wheals may coexist with intact bullae, and hemorrhagic bullae are not unusual. Lesions occur most often on the trunk and proximal extremities and show a predilection for flexural surfaces; approximately one third of patients have oral blisters, although, unlike the situation in pemphigus vulgaris, the mouth is rarely the initial site of involvement. In some patients, bullae remain localized to one area for several months, and in a few, the lesions never become widespread. The diagnosis is confirmed by skin biopsy. Immunofluorescent staining of perilesional skin, which is virtually pathognomonic, shows linear deposition along the basement membrane zone of C3 (third component of complement) in all patients and of IgG in most. Indirect immunofluorescent studies demonstrate anti-basement membrane zone antibodies of the IgG class in approximately 70% of patients.39
Figure 43-2 Bullous pemphigoid involving the axilla and medial arm. Note numerous tense bullae and scattered hemorrhagic erosions. (Courtesy of K. Arndt, M.D.)
A 230-kD protein and a 180-kD protein, referred to as the bullous pemphigoid antigen 1 and the bullous pemphigoid antigen 2, respectively, are implicated as the targets for antibody binding in patients with BP. These two antigens are components of the hemidesmosome,40 which attaches the basal keratinocyte to the basement membrane. Thus, when this attachment is disturbed, dermoepidermal separation and blister formation ensue.
Corticosteroids are the gold standard of therapy. In mild or localized cases, topical or intralesional steroid application may control the lesions, but almost all patients require systemic treatment at least initially. Patients with extensive or rapidly progressive disabling disease should begin therapy with prednisone, 60 to 100 mg daily (some authors recommend two to three times this dose). Patients should be reevaluated at weekly intervals and the prednisone dose progressively reduced once new blisters have ceased forming and clinical remission has been achieved. An immunosuppressant, such as azathioprine, cyclophosphamide,39,41 or methotrexate,42 may be added to the regimen initially or at the time of remission to reduce the eventual maintenance level of prednisone. Six to eight weeks are required for full expression of the steroid-sparing effect. In patients with less severe disease therapy may be initiated with 40 to 60 mg of prednisone on alternate days and/or an immunosuppressant. Drug dosages are decreased gradually to zero over many months, provided the disease remains in remission. Sulfapyridine or sulfones may be valuable alternative therapies for patients with major contraindications to systemic steroids. Recently, investigators have reported successful therapy with high-dose tetracycline (500 mg four times a day) and nicotinamide (500 mg three times a day).43 In most patients prolonged remissions are achieved, and in at least half, treatment ultimately can be discontinued without recurrence of lesions. However, frequent exacerbations of bullous pemphigoid and potential complications of therapy require close monitoring of all patients throughout the course of their disease.