The prevalence of skin disorders in AIDS patients treated in the palliative care setting is exceptionally high. Unfortunately, accurate diagnosis and proper treatment of skin diseases in both HIV and AIDS can be an especially challenging and often frustrating task, because the presentation of common dermatoses is often exaggerated into florid cutaneous eruptions. The practitioner also has to be cognizant of more unusual cutaneous disorders that would otherwise be virtually nonexistent in his or her daily practice. Furthermore, because of the severe immunosuppression seen in end-stage AIDS patients, treatment and eradication of these disorders is almost always difficult, and often not possible. In these instances, appropriate palliative care needs to be administered in a timely fashion to assure a better quality of life for these patients.
The health care provider will need to be aware of the following in caring for AIDS patients in the palliative care setting who develop skin disorders.
- Many common dermatoses may have unusual or unusually severe presentations in HIV disease, and especially in advanced and end-stage AIDS.
- The hospice environment predisposes patients with AIDS to certain skin conditions. This is attributable not only to severe immunosuppression, but also to immobilization, bed confinement, and close quarters.
- It is important to recognize primary skin lesions, and to differentiate those from cutaneous changes associated with manipulation and trauma to the skin, such as scratching, picking, and rubbing. These are seen in most patients with advanced HIV disease, as a consequence of severe, chronic, and intractable pruritus.
- A thorough skin examination must be done whenever possible and should be performed under good lighting, with the patient completely undressed. Examine the whole body including scalp, hair, oral mucosa, and nails. It is of utmost importance to note the pattern of distribution of the lesions and areas of sparing and to determine the predominant type of lesion.
- Simple auxiliary tests done on scrapings of the skin can be diagnostic and are extremely helpful in narrowing down the differential diagnosis. They should be performed as often as possible and whenever a microscope is available. These tests include KOH prep of every scaly lesion, Tzanck smear of any ulcerated or bullous lesion, and mineral oil prep of generalized pruritic papules or whenever the clinical morphology or epidemiology are suggestive of scabies. Cultures for bacteria, fungi, mycobacteria, and viruses should always be obtained whenever clinical findings suggest an infection.
Keeping these ideas in mind and armed with the knowledge of the most common cutaneous manifestations of advanced HIV infection, the AIDS hospice practitioner will be better prepared to identify cutaneous infectious processes, and to differentiate these from neoplastic or inflammatory skin conditions.
The incidence, prevalence, severity, and clinical appearance of cutaneous diseases vary significantly with the transition from asymptomatic HIV infection to the development of AIDS. Although successful treatment with antiretroviral regimens helps to control many of the cutaneous disorders, certain skin conditions may actually flare when treatment is effective and a phase of immunologic recovery develops. Proper understanding of the epidemiology of AIDSrelated cutaneous disorders can aid in anticipating conditions that may arise, and can hasten appropriate diagnosis and treatment measures to enhance the patient’s quality of life. The types of disorders range from infectious processes to malignant conditions and inflammatory disorders to conditions directly related to immobility and the hospice environment.
Several studies throughout the world have documented with many similarities the most prevalent cutaneous findings that occur as a patient transitions from asymptomatic infection through AIDS and finally reaches the terminal phase of the disease. One study found that the prevalence of any skin disorders in the HIV-positive population was 91%, with an average of more than two simultaneous conditions per patient. While xerosis (dry skin) was a common finding irrespective of disease stage, the infectious processes including fungal, bacterial, and viral disease as well as inflammatory conditions such as eczema, pruritus, and psoriasis were increasingly more common when matched with the degree of immunosuppression. Additionally, infestations such as scabies and malignancy, specifically Kaposi’s sarcoma (KS), were more prevalent with fulminant AIDS and the associated dramatically decreased CD4 counts.1
Although there has been some disagreement between various epidemiologic studies, there have been a few consistent results. Specifically, there seems to be a much higher incidence of infectious, inflammatory, and neoplastic conditions as one transitions from HIV to fulminant AIDS. There have been varied reports on the incidence of bacterial infection.2 One very important factor that changes the incidence of certain types of cutaneous disorders is demographics. Geographic location as well as patient population (i.e., intravenous drug users (IDU), impoverished inner city patients, or homosexual males) dictate the development of some very different conditions. For example, when comparing Uthayakumar’s1 cohort of 92% homosexual men to another study made of 74% IDU and only 9% homosexual men, there was a clear distinction in the incidence of KS between the two populations with a significantly lower incidence in the IDU population.3
Another issue borne out from the various demographic studies is the lack of correlation between absolute CD4 counts and the development of certain cutaneous disorders. While there is some consistency between development of cutaneous conditions with the general health and immunologic state of the patient, the standard deviations seen in CD4 counts at the time of diagnosis of many conditions were so large that statistical significance was lost.3 In addition, many inflammatory conditions, which would normally be associated with a healthy, overactive immune system, are seen more frequently in the profoundly immunocompromised. Although it may seem intuitive to think of end-stage AIDS as equivalent to a nearly complete lack of immunity, these patients suffer from a severe, “cytokine haywire” that causes a state of cutaneous hyperreactivity responsible for the many inflammatory conditions including pruritus and the many forms of eczema.
• Back to Top •Pruritus, or the sensation of itching, is the most common dermatologic symptom and it can, at times, be so severe as to drive patients to developing suicidal thoughts. Unfortunately, but not surprisingly, it is also the most common dermatologic problem in patients with both HIV and AIDS. With this in mind, accurately diagnosing a pruritic eruption becomes a daunting, yet necessary task because the pruritus can cause significant morbidity.
Pruritus can be localized or generalized and is often associated with a state of hypereosinophilia. It can be caused by skin lesions or rashes or it can indirectly induce the development of skin lesions due to trauma, such as from scratching and rubbing. To establish the etiology of the pruritus, the practitioner should first attempt to identify any primary skin lesions and then follow a rather simple diagnostic algorithm. Examples of types of primary lesions that one commonly encounters with pruritic eruptions are papules or nodules (“bumps”), plaques (slightly elevated, palpable lesions with large diameter), and exanthems (diffuse or patchy “redness” of the skin). Very commonly one sees combinations of different types of lesions that may or may not be associated with surface changes, such as scaling, crusting, or ulceration.
The clinical presentation of pruritus is widely variable because of its many potential etiologies (Table 9-1). Localized pruritus is usually associated with primary skin lesions, i.e., papules and burrows of scabies or scaling plaques of tinea corporis. However, generalized pruritus may or may not be associated with primary lesions. For example, pruritus associated with obstructive biliary disease may only demonstrate excoriations, but generalized xerosis cutis shows widespread drying, cracking, and fissuring of the skin, which is responsible for intense itching. Unfortunately, in the terminal stages of AIDS, patients often suffer from cutaneous disorders representing a combination of multiple pathologies. Often, in addition to xerosis, there may be adverse drug reactions, liver failure, and multiple infections, which all result in potentially unbearable pruritus, making diagnosis and palliative treatment very difficult.
Lichen simplex chronicus is a pruritic condition produced and aggravated by scratching or rubbing. The underlying etiology is not well understood, and some have postulated a sensory neuropathy whereas others maintain a psychological origin. Inciting factors may include any bites, trauma, or pruritic skin disorders. Prurigo nodularis (Color Plate 9-1), a nodular variant of lichen simplex chronicus is also perpetuated by rubbing and/or scratching. Either hyper- or hypopigmented nodules are often seen on a background of accentuated skin markings and pronounced skin thickening.
A common consequence of prolonged pruritus and scratching is postinflammatory pigmentary changes. There is often a racial predilection for these changes in that African Americans very frequently develop hyperpigmented lesions after resolution of the active disease process. These changes may be so extensive and cosmetically disfiguring as to cause significant anxiety in the patient. Pruritus itself is both an anxiety-inducing disorder and a consequence of anxiety in that anxiety and related mood disorders help to propagate the vicious cycle of itching, scratching, and itching again. Anxiety and depression, both psychiatric conditions inextricably linked to terminal disease, lower the threshold for pruritus.
Apart from the requisite thorough medical history, the physical examination will generally guide diagnosis. The following diagnostic algorithm (adapted from Majors and co-workers4) represents a simplified way of approaching the diagnosis of pruritic eruptions based primarily on their morphology. The first question to be asked is: “Are primary lesions present?” That is, are there intact papules, vesicles, or plaques that have not yet been manipulated by the patient? Are there skin lesions other than those caused by scratching, picking, or rubbing?
If all the cutaneous findings represent the result of scratching or rubbing of the skin, then two main diagnostic alternatives exist: the pruritus either is from systemic disease or is psychogenic in origin.
At different stages of HIV infection, pruritus can be the direct result of viral infection. For example, the initial manifestation of very early infection, far before overt AIDS takes control, the patients often suffer from a transient, influenza-like illness that may be associated with a morbilliform eruption. This may be pruritic in nature. Additionally, as the patients succumb to the devastating immunologic attack of fulminant AIDS, they suffer from a severe immunologic imbalance. Despite the fact that CD4 counts have plummeted, cytokine production is drastically dysregulated and often causes generalized pruritus.
Other systemic causes of pruritus are renal failure, obstructive biliary disease, hyper- or hypothyroidism, diabetes mellitus, multiple myeloma, carcinoid, polycythemia vera, lymphoma, or anemia. To rule out these diagnoses a basic workup is recommended as outlined in the section below, Objective Data, below. Otherwise, appropriate psychiatric evaluation and treatment are indicated.
Once established that a primary cutaneous disease process does exist, the next step would be to determine whether these lesions are associated with hair follicles. One simplified way of doing so is to try to identify the follicular ostium (“pore”) at the center of each individual lesion. Another way of assessing if they are follicular is to see if the lesions are roughly equally spaced on the affected areas, since hair follicles do have a homogeneous distribution on any given skin area.
Once it is determined that the lesions are associated with hair follicles, a short differential diagnosis is available and includes folliculitis, acne, and rosacea.
The remaining primary nonfollicular, pruritic lesions should then be grouped into two main groups: papular/nodular lesions and the scaly/papulosquamous eruptions. Diagnosis of papular nonfollicular primary lesions most commonly includes scabies, insect bites and papular urticaria, drug eruptions, miliaria, and Grover’s disease (discussed in section on Skin Problems in the Chronic, Bedridden Patient on page 198). The most frequently encountered scaly/papulosquamous eruptions are xerosis cutis, asteatotic eczema, seborrheic dermatitis, dermatophyte infections, and psoriasis, which are differentiated by the extent of disease, the quality of the scale, location, and degree of associated inflammation (discussed in section on Eczemas and Papulosquamous Disease on page 183).
In patients with HIV, a thorough skin examination will reveal, in most cases, at least one possible dermatologic cause for the pruritus. In these cases, the skin condition should be treated before an expensive workup for possible systemic causes of pruritus is done, because clearing the skin problem very often clears the pruritus as well.
The laboratory investigation for internal causes of pruritus in the absence of primary skin pathology and neurologic disease is the same for AIDS patients as it is for the immunocompetent individual. A complete blood count with manual differential can exclude anemia, polycythemia vera, or lymphoproliferative disorders. Liver function tests can rule out obstructive biliary processes. An electrolyte screen that includes blood urea nitrogen, creatinine, and glucose levels excludes renal insufficiency, uremia, and diabetes. Thyroid-stimulating hormone and parathyroid hormone are good primary screens for thyroid and parathyroid disorders.
As previously mentioned, the first step is to treat any primary dermatologic process. In cases associated with a systemic disease, cure of the underlying systemic process is frequently impossible, therefore therapy is aimed at achieving and maintaining symptomatic relief only. Some general guidelines should be followed, keeping in mind that the main goal is to break the itching/scratching cycle, because scratching induces more pruritus, thus perpetuating and intensifying the problem. Some measures that may help most patients with pruritus are discussed below.
- Modification of showering and bathing habits, advocating the importance of taking no more than one shower a day, avoiding hot showers, using soap very sparingly, preferably on the intertriginous areas only, and not using any abrasive material such as washcloths, sponges, etc.
- Adequate moisturization of the skin with daily or twice-daily applications of emollient lotions or creams to prevent or correct xerosis cutis, one of the most common causes of pruritus in patients with advanced HIV disease.
- H1-blocking oral antihistamines, used as a single agent or as combination of a sedating type at night and a nonsedating type (second-generation H1 blockers) in the morning. Usually patients are kept on maximum doses around-the-clock if significant relief is desired.
- Topical antipruritic agents compounded in moisturizing creams or lotions applied to the most affected areas as often as needed. Most commonly used agents are menthol (0.25%), phenol (0.25%), Doxepin, and Pramoxine.
- Mid- to high-potency topical corticosteroid preparations should be used to treat individual lesions of prurigo nodularis and lichen simplex chronicus. These can also be compounded with any of the anti-pruritic agents as described above. (See Table 9-2)
Harder to control cases can be successfully treated with phototherapy, using either ultraviolet B light or ultraviolet A plus psoralen, a photosensitizing agent, in a regimen known as PUVA. However, this method requires a specialized dermatologic facility and significant commitment to a schedule of treatments administered three times a week for a minimum of 3 months, and is therefore not a practical option for most hospice patients.
Intractable pruritus can be successfully controlled with thalidomide but because of its significant and potentially serious side effects, thalidomide should be used only in selected patients. Thalidomide should be started at 100 mg qd for one to two weeks followed by 200 mg qd. Regular blood tests including complete blood count and viral load should always be obtained while the patient is on this medication. Also one should monitor closely for development of side effects, including neuropathy.
• Back to Top •Eczema is the most common inflammatory disorder of the skin and, in any of its subtypes, generally presents in one of three stages, i.e., acute, subacute, or chronic. These forms are characterized by varying degrees of erythema, vesiculation, crusting, scaling, hyperpigmentation, and skin thickening. Examples of eczemas commonly seen in individuals with HIV are asteatotic, atopic, seborrheic, nummular, and contact dermatitis.
The papulosquamous diseases of the skin are manifold, but have in common their primary morphological characteristics, namely scaling papules and plaques. Common examples of these diseases are psoriasis, pityriasis rosea, and xerosis cutis. The papulosquamous and eczematous dermatoses can affect both HIV-negative and HIV-positive individuals, but, as previously mentioned, their clinical presentation can be drastically altered with advancing immunosuppression.
Also known as eczema craquele (Color Plate 9-2), asteatotic eczema is caused by, and therefore usually seen concomitantly with, xerosis cutis generalisata (severely dry skin). Both conditions are the most common dermatoses seen in individuals with advanced HIV, particularly during the winter months, when the degree of humidity in the environment is significantly lower. Dryness of the skin (xerosis) is accompanied by the development of microscopic tears on the skin surface, causing initially subclinical inflammation, intense pruritus, and subsequently evolving into overt eczema. This condition is usually one of the first papulosquamous/eczematous eruptions to develop, usually presenting early when the CD4 counts drop below 400 and, as the HIV disease progresses, it becomes more generalized, more symptomatic, and more difficult to treat.
The usual presentation is with xerosis of the skin, characterized by scaling and varied degrees of superficial fissuring, affecting especially the lower extremities. When significant disruption of the skin barrier is present, serous oozing and resultant crusting is seen. The combination of pruritus and disruption in the skin barrier leads to a significantly higher risk for secondary bacterial infection. When severe, pain rather than pruritus may be a more common symptom. The signs of frank cellulitis, namely erythema, edema, pain, and purulent exudate, should be identified before bacteremia and sepsis ensue.
Atopic dermatitis, nummular eczema, seborrheic dermatitis, psoriasis, crusted (“Norwegian”) scabies, generalized inflammatory reaction to skin infections such as dermatophytoses.
Treatment depends on the extent of disease at presentation. First and foremost, it must be determined if an overlying bacterial infection is present. If secondary infection is noticed, crusts should be removed with wet compresses and appropriate oral antibiotics covering common skin pathogens should be given. When infection is not an issue, then generous use of emollients and keratolytic agents such as urea, salicylic acid, and lactic acid should be given. Although often ineffective, H1 blockers should be tried to reduce itching and the inevitable associated excoriation. For clearly inflammatory lesions, midpotency topical corticosteroid preparations should be used. Saturated fatty acid soaps, such as Emulave and Basis, should also be used, again with copious lubrication after bathing.5
This common condition often presents a diagnostic dilemma because of its resemblance to tinea corporis, pityriasis rosea, and psoriasis, three conditions that are also commonly seen in the AIDS patient. The course of disease is usually a chronic one, with many cases unresponsive to therapy.
Pruritic, well-demarcated, erythematous, round plaques, usually 1 to 5 cm in diameter, with scales and/or crusts over the entire surface of the lesion (Color Plate 9-3). Nummular eczema is the perfect example of how exacting attention to detail in description of the lesional morphology will help pinpoint accurate diagnosis. The scales are usually mixed with crusts, as opposed to psoriasis, which has heavy, silvery scale. This is also different from tinea corporis, which shows scaling at the periphery and central clearing, giving it the appearance of a “ring,” and pityriasis rosea, which has a “collarette” scale just behind the advancing border of the lesion.
A KOH prep must be performed to exclude multifocal tinea corporis (ringworm). Other differentials are plaque-type psoriasis and atypical pityriasis rosea.
Mid- to high-potency topical corticosteroids used twice daily only on the lesions, in conjunction with H1-blocking antihistamines, are the mainstay of therapy. For diffuse disease, caution must be taken when applying potent topical steroids over large body surface areas, because systemic absorption does occur, and with long-term use, the potential for suppression of the pituitary axis exists.
Atopic dermatitis can flare in individuals with an atopic background and HIV infection, even after decades of complete remission. As with any of the eczemas, it may present features of acute, subacute, or chronic skin inflammation but, in the terminally ill patients, chronic features of lichenification, hyperpigmentation, and/or hyperkeratosis prevail.
The most common presentation of atopic dermatitis in HIV-negative adults is chronic, recurrent dermatitis localized to either the palms and soles, ankles and elbows, or popliteal and antecubital fossae. In HIV-positive individuals, immunologic dysregulation favors frequent outbreaks, which are initially localized or multifocal, but usually become widespread and generalized in patients with advanced disease. The clinical features in subacute stages are mild to moderate erythema, crusting, hyperkeratosis, and scaling. Chronic lesions are characterized by secondary changes resulting from manipulation, namely rubbing and scratching. Skin then becomes thickened, darkened and rough with accentuation of the superficial skin markings. Atopic dermatitis is a particularly pruritic type of eczema and when it becomes chronic, excoriations, crusting, and scarring develop as a result of scratching. Commonly affected areas include the face, neck, trunk, flexural surfaces of the extremities, extensor surface of the forearms and lower legs, dorsal and plantar surfaces of the feet, and palms and dorsum of the hands (Color Plate 9-4).
Seborrheic dermatitis, eczematous drug reaction, contact dermatitis, crusted (“Norwegian”) scabies, widespread impetigo.
Topical corticosteroid preparations or the recently introduced topical tacrolimus 0.1% ointment (Protopic) should be used to reduce inflammation. Potent corticosteroids (Class III) may be needed at first to gain control of this intensely pruritic condition and then tapered to more mild steroid agents. Antihistamines such as diphenhydramine or hydroxyzine are very helpful, especially at night. Careful monitoring of the skin for signs of secondary bacterial infection is very important. Skin dryness aggravates atopic dermatitis immensely; therefore, liberal use of emollients and soap avoidance are mandatory. Colloidal oatmeal baths followed by widespread application of petroleum jelly daily is also very helpful to control pruritus. Patient education to avoid scratching and rubbing is also needed.
Seborrheic dermatitis very often becomes a more florid eruption in AIDS than that seen in the general population, with the extent of disease inversely proportional to the patient’s gross CD4 level. Although the incidence of seborrheic dermatitis affecting nonscalp skin in the general public has been estimated at less than 5%, some studies have documented a prevalence of 40% to 80% in AIDS. The follicular yeast Pityrosporum ovale appears to play a role in the development and maintenance of skin lesions, but it represents only one of multiple factors that may be involved in the pathogenesis of this type of eczema.
Although seborrheic dermatitis presents in healthy persons as an erythematous, greasy scaling/crusting eruption, usually localized to the nasolabial folds, ears, eyebrows, forehead and scalp, the eruption in AIDS can be much more extensive. The erythema is significantly more pronounced and diffuse. Scales are thicker and more greasy, and can resemble those seen in psoriasis. The skin surface involved is extended past the face and scalp to involve the presternal area, axillae, groin, genitals, and buttocks.
Atopic dermatitis, contact dermatitis, eczematous drug eruption, intertrigo, and inverse psoriasis.
Inflammatory lesions on the face can be treated with low-potency (Class V) topical corticosteroid creams and lotions or more potent preparations, depending on the location and degree of inflammation. They should be applied twice daily. Facial skin is very thin and susceptible to the damaging effects of long-term use of superpotent topical steroids (telangiectasias, atrophy, striae, discoloration); such steroids, therefore, should be used only as a temporizing measure. Ketoconazole 2% topical cream, lotion, or shampoo, or 200–400 mg of ketoconazole orally per day should be tried because it has been shown to be a treatment successful in 25% of cases.6 Tar and salicylic acid-based shampoos are helpful in cases associated with thick scaling plaques on the scalp.
Psoriasis occurs in approximately 1% of the population worldwide. Its prevalence in HIVinfected individuals is not significantly greater than this, but its presentation is often atypical and more widespread. Not uncommonly, the abrupt development of widespread psoriasis as an adult without prior history of the disease is the first manifestation of HIV infection.
Psoriasis can develop in one of two forms, namely localized lesions or generalized disease. The typical lesion is a well-circumscribed, erythematous plaque with thick, “silvery” scales that are easily detached, leaving a bright pinkish/red base (Color Plate 9-5). The most common location is on the areas of pressure and trauma such as the extensor surfaces of the extremities, sacral area, hands, feet, and scalp. In patients with AIDS, however, psoriasis usually presents as a generalized eruption. Most commonly generalized plaques, but more atypical forms such as erythrodermic and pustular psoriasis, as well as psoriasis associated with severe arthropathy are frequently seen.
Localized disease: atypical pityriasis rosea, nummular eczema, tinea corporis; widespread disease: seborrheic dermatitis, disorders causing erythroderma including dermatomyositis and lymphoproliferative disease.
Treatment of generalized disease usually requires some form of systemic therapy, but it often becomes a difficult issue because of the immunosuppression and/or liver or renal toxicity that can be associated with most of the systemic drugs available. Examples of these therapeutic modalities are the immunosuppressive agents methotrexate and cyclosporine as well as oral retinoids such as acitretin, and biologic response modifiers such as specific monoclonal antibody therapy. Phototherapy using ultraviolet B alone or PUVA are both associated with very good response rates. Unfortunately, these are not practical options for patients in the hospice setting because these treatments require transportation to a facility that has the appropriate equipment, three times a week, for a prolonged length of time.
Topical therapy therefore is the therapeutic modality of choice for most of these patients. Mid to high-potency (Classes I, II, or III) topical corticosteroid preparations, coal tar products, vitamin D derivatives such as calcipotriol, and vitamin A derivatives such as tazarotene can all be tried. Again, regular emollient use is a very helpful adjuvant measure.
Inflammation of the hair follicle usually indicates an infection of the pilosebaceous unit. In AIDS, infections with Staphylococcus aureus are very common but additionally organisms that are part of the normal flora in the hair follicle such as Pityrosporum yeasts (P. ovale) or Demodex mites (D. folliculorum) can induce a very pruritic process characterized by eosinophilic inflammation. In many instances, an infectious agent cannot be identified and biopsy of the skin lesion reveals destruction of the hair follicle by a dense eosinophilic infiltrate, known as eosinophilic folliculitis. It has been estimated that 25% of the pruritic conditions of advanced HIV disease represent some type of folliculitis and these prevalence rates can increase during the summer months. In patients receiving chronic antibiotic prophylaxis, a gram-negative folliculitis may also develop. Another type of noninfectious folliculitis commonly seen is that associated with hormonal therapy, mainly testosterone and anabolic steroids as well as growth hormone replacement therapy.
S. aureus folliculitis is usually caused by cutaneous spread from nasal carriage, which is twice as common in HIV-positive people than in healthy control subjects. The presentation can be varied, but typically consists of erythematous follicular papules and pustules somewhat equally spaced on the skin surface, but may be clustered in some areas. Lesions in different stages present at the same time, with pustules, crusts, and varying degrees of inflammation and are very suggestive of a bacterial process. Monomorphic superficial pustules are more typically seen in folliculitis caused by yeasts, whereas significant edema of individual papules (“juicy” appearance) with signs of aggressive excoriation are more suggestive of either a parasitic or an eosinophilic process. In cases of bacterial folliculitis, depending on the degree of inflammation and the depth of penetration into the follicle, a painful, erythematous nodule may develop, called a furuncle or boil.
Eosinophilic folliculitis usually presents when CD4 counts drop below 200. It presents with urticarial papules usually confined to the upper trunk, face, scalp, and neck, and it can uncommonly also be pustular. The course waxes and wanes and can be characterized by unpredictable flares. There is usually an associated peripheral eosinophilia and elevated levels of IgE.
Clinical diagnosis alone is difficult for the untrained care provider, therefore lesions should be biopsied and sent for culture and histopathology, specifically requesting special stains for different infectious organisms.
In the absence of available tissue for histopathologic examination, it is acceptable to empirically treat based on a “shotgun” type approach. If forced into such a circumstance by the inaccessibility of a biopsy, coverage for fungal elements, bacterial pathogens and Demodex, in addition to treating the inflammatory component, is required. In such a regimen, ketoconazole 2% lotion applied qd to bid, erythromycin 2% gel applied bid with or without 10% benzoyl peroxide and metronidazole 0.75% lotion applied bid cover fungal, bacterial and Demodex, respectively. Any non-fluorinated steroid of choice used bid is appropriate to control inflammation. In the presence of diagnostic biopsy demonstrating a predominance of either fungal or bacterial or Demodex responsible for the eosinophilic inflammation, treatment modalities should reflect the histopathologic diagnosis.
However, in the absence of a biopsy, a “shotgun” approach is not always necessary. In many situations, the clinical history and appearance of the lesions can guide a more directed approach to therapy. Clinically obvious bacterial folliculitis should be treated with topical antibiotics and benzoyl peroxide combinations. Clindamycin/Benzoyl peroxide as well as Erythromycin/Benzoyl peroxide combinations are very useful for limited areas. For larger treatments, a benzoyl peroxide wash is helpful. In addition, antibacterial soaps help to reduce colonization by skin flora. If furunculosis is present, then oral antibiotics are required, directed against gram-positive bacteria. If a bacterial folliculitis develops while already on oral antibiotics, then gram-negative folliculitis should be suspected and treated with Trimethoprim-sulfamethoxazole. Extensive, pustular and cystic bacterial folliculitis can be treated with the oral retinoid, isotretinoin. However, there is significant potential morbidity due to the many possible side effects that are often tolerable only in the immunocompetant host. The potential for liver toxicity, cytopenias and excessive dryness of the skin and mucous membranes, to name a few, make oral isotretinoin a far less attractive therapeutic option in AIDS hospice patients.
If the clinical picture suggests a folliculitis of fungal etiology, ketoconazole cream or shampoos are helpful. If extensive or recalcitrant to a two-three week course of aggressive topical therapy, then oral antifungals should be used. Demodex folliculits should first be treated with topical metronidazole, or permethrins. Often, if a clinical overlap exists, then a combination regimen using two or more of the above topical medications may hasten clinical remission.
Bacterial infection most commonly represents secondary penetration of skin flora as a result of barrier disruption due to severe xerosis, eczema, or by direct penetration. The gram-positive organisms, both Strep and Staph genera, are responsible for impetigo and ecthyma as well as recurrent cellulitis.
Erythematous, minimally elevated papules covered by honey-colored thin crusts. May be limited to one or a few lesions or may be multiple, coalescing into crusted plaques. Ecthyma is a more localized and clearly a deeper process, presenting with more induration, erythema, and edema with the development of a thick eschar that heals with scarring.
More commonly encountered on the lower extremities, there is a poorly defined patch of erythema surrounding the site of initial penetration by bacteria. At that site, pus and crust are often present. Peripherally from this lesion, one may see erythematous streaking, suggesting lymphangitic spread of bacteria. The involved region is also painful and warmer than on the opposite leg. As a general rule, bilateral lower extremity cellulitis does not exist. Cellulitis is differentiated from erysipelas as follows: Erysipelas shows a very indurated, tense lesion with a well-demarcated, elevated border that more commonly occurs on the head and neck region.
Culture is generally not necessary and typically yields the expected pathogenic skin flora. Sensitivities will be useful, however, in disease that is recalcitrant to treatment to investigate antibiotic resistance profiles.
Mupirocin 2% (Bactroban) ointment or cream tid-qid until clear. This is usually effective in treating mild and localized disease. Systemic therapy is indicated in cases of bullous impetigo, extensive disease or with regional lymphadenopathy. The preferred treatment for nonbullous impetigo is either penicillin VK 250-500 mg PO q6-8h x 7d, penicillin G-benzathine 1.2 million U IM x 1, amoxicillin 250-500 mg PO q8h or 500-875 mg PO q12h x 7d, or ampicillin PO q6h x 7d. For bullous impetigo or culture-proven Staphylococcal impetigo either cephalexin 250-500 mg PO q6h x 7d, cefadroxil 500 mg-1g PO q12h x 7d, or dicloxacillin 500 mg PO q6h x 7d. In addition to the aforementioned antibiotic regimens, practitioners should soften the crusts with clean Vaseline or Bacitracin ointment several times per day, wash the individual lesions with antibacterial soap or antiseptic solution and water, trying to gently remove crusts twice a day, instruct the patient not to touch the lesions and to wash hands frequently, and clip fingernails short to decrease risks of excoriation, self-inoculation, and contagion.
While penicillin is, in most cases, appropriate for the treatment of uncomplicated streptococcal cellulitis, the problem of resistance is very real. Keeping this in mind, a penicillinase-resistant penicillin (e.g. dicloxacillin 250-500 mg PO qid) or first generation cephalosporin (e.g. cephalexin 250-500 mg PO qid) may be used. These also should be kept in mind for Staphylococcal genera. However, mild cases of non-resistant Streptococcal cellulitis may be treated with penicillin V 500mg PO q6h x 10d or penicillin G benzathine 1.2 mil U IM x1. If penicillin allergic, then Erythromycin 250-500mg PO q6h or 333mg PO q8h x 7-10d or azithromycin 500mg PO x1 followed by 250mg PO qd x 4d or clarithromycin 250mg PO q12h x 7-10d. For severe cases, penicillin G 2-4mil U IM or IV q4-6h (maximum 24mil U/day) is suggested.
Other interventions besides antibiotics include immobilization and elevation of the affected area, moist heat compresses, and debridement and drainage when bullae, abscess or necrosis is present.
Viral infections tend to run rampant in patients with advanced HIV disease. Not only are Herpes simplex infections the most commonly seen in this setting, but Varicella zoster virus reactivation as well as poxviruses and human papillomavirus infection are all especially common.
Herpes labialis often begins with a prodrome of pain or burning on the lip prior to eruption of a tender, vesicular, erythematous lesion that crusts in a few days. In advanced HIV infection, the lesions may be chronic, difficult to eradicate, often resistant to standard antiviral therapy, and may become more extensive, often involving not only the lip but part of the cheek as well, making diagnosis more difficult.
Seen in both the healthy and AIDS populations, genital herpes presents with either shallow, clean, superficial ulcers on an erythematous base or with a patch of erythema with a cluster of vesicles that later ulcerate. These lesions are also painful. In advanced AIDS, the chronic, extensive perianal lesions may provide a diagnostic challenge (Color Plate 9-6). As ulcers become confluent and the associated patches of erythema larger, they often resemble Candida intertrigo and irritant contact dermatitis from chronic diarrhea. Again, careful examination is paramount to accurate diagnosis and treatment because antifungal agents will not help and topical steroids will make the infection much worse. Candidal intertrigo usually involves the entire perineum, not simply the perianal region, characteristically has peripheral satellite lesions, and ulceration is not a feature. In addition, chronic diarrhea and incontinence should cause perianal irritation and maceration, but there should not be large regions of ulceration unless there is also associated decubitus ulcer. In such cases, it is always best to swab the ulcer base for viral culture.
Painful, tender, erythematous patch on the distal phalynx of usually one finger. Whitlow is the result of direct inoculation of the finger from another site and before AIDS was more commonly seen in health care workers as a consequence of direct, ungloved contact with a patient’s herpetic lesion.
Reactivation of the varicella zoster virus (VZV) from the dorsal root ganglia of spinal nerves is a painful sequella to AIDS-related immunosuppression. Following a dermatomal distribution, a strikingly erythematous cluster of papules forming a plaque with overlying vesicles is often present in a patch- or band-like configuration. The presentation in normal hosts is one in which any significant portion of the rash rarely crosses the midline. However, in the AIDS group, zoster may be more inflamed and painful and may be disseminated. Chronic and recurrent forms may also become an issue. Burning pain may either precede the cutaneous eruption or may continue after the acute episode as postherpetic neuralgia. The postherpetic neuralgia is a cause of significant morbidity, as the intense burning pain can last for years after the cutaneous lesions have gone and is often very difficult to treat, especially in this population. Involvement of the tip of the nose signifies involvement of the ophthalmic branch of the trigeminal nerve and heralds a potential ophthalmic emergency, termed zoster ophthalmicus. In AIDS patients receiving chronic acyclovir therapy, acyclovir-resistant VZV infection may present with a chronic, disseminated form of Zoster. The lesions are warty, hyperkeratotic papules with or without ulceration or eschar formation.
A contagious viral infection previously seen predominantly in children, this previously benign condition can occasionally have devastating consequences in AIDS.
The usual presentation in both normal children and adults with AIDS is that of scattered skin-colored, dome-shaped papules, approximately 3 mm in diameter with a central dimple, or umbilication. The lesions can be a few in number or be present in hundreds, covering large areas of the body, commonly the face and neck, with devastating impact on the patient’s quality of life.
Less frequently, in the immunocompromised patient giant molluscum may ensue with larger papules that appear in a cluster and aggregate into large fungating plaques (Color Plate 9-7).
Different serotypes of the human papillomavirus (HPV) dictate where a wart will arise on the body. Verruca vulgaris, or common warts, are frequently seen in both the general population and in AIDS patients. They are difficult to eradicate in both groups. Condyloma accuminata, or genital warts, flourish in the immunosuppressed host and may reach very large sizes, presenting as warty, cauliflower-like growths in the perineal region. Flat warts do occur in the normal host, but tend to flourish in the immunocompromised. They appear as groups of hypopigmented, flat-topped, regularly shaped 2 to 4 mm papules that, at times may be so flat as to appear macular. Condyloma accuminata are generally associated with HPV serotypes 6, 11, 16, and 18. There is a significantly increased risk for the development of squamous cell carcinoma when the lesions are associated with HPV types 16 and 18. Anogenital veruccae are often difficult to visualize without anoscopy and, unfortunately, may cause the most significant morbidity, as very large growths may partially obstruct the anal canal.
Most of the aforementioned disorders are diagnosed strictly on clinical grounds; however, viral culture and serotyping can be an important tool for not only confirmation of the clinical suspicion but also for viral sensitivity profiles, because resistance is not uncommon. If the diagnosis is uncertain, then a simple punch biopsy of the lesion in question can also aid in diagnosis. A Tzanck smear for HSV can be performed in the office if vesicles or fresh ulcers are present. Old, previously unroofed blisters or ulcers will not suffice. Using a sterile scalpel blade and a sterile swab, the intact blister roof is removed and the base of the blister is aggressively scraped. (Extraction of the blister fluid alone is insufficient for the Tzanck smear.) Once the base is swabbed, the cells are rubbed onto a microscope slide and the specimen is rapidly fixed and stained in the office prior to microscopic examination looking for multinucleated giant cells. During the same procedure, a culture may be taken from the same denuded blister.
The approach to treating herpes labialis, genital herpes, and herpetic whitlow are very similar. Previous initial therapy utilized acyclovir, a cumbersome regimen that required five daily doses which, in combination with other AIDS regimens, raises compliance issues. Therefore, valacyclovir (Valtrex) is generally the preferred starting regimen for uncomplicated HSV. A dosing regimen of 1 g bid for 7 to 10 days should be tried first. For widespread or nonresponsive forms of HSV, intravenous acyclovir should be used and cultures should be obtained for sensitivity. Resistance is common and other drug regimens such as foscarnet should be used for resistant herpes.
For uncomplicated Zoster, the same generalized initial treatment guidelines as for HSV apply. However, Zoster ophthalmicus and the more complicated forms of generalized zoster require hospitalization and intravenous acyclovir. Zoster ophthalmicus requires emergency consultation by ophthalmology.
Uncomplicated molluscum is more of a nuisance and cosmetic problem that is common in the AIDS population. Although there is no permanent cure, it can be easily controlled with local destructive methods and immunomodulatory agents. The key is not allowing the infection to run rampant. Localized, minimal disease can be treated with cryotherapy, electrocautery, blister beetle extract (cantharidine), cidofovir, or the immunomodulator imiquimod 5% cream, applied 3 nights per week. However, giant molluscum is very resistant to all known therapies. Cryotherapy, CO2 laser, tretinoin and trichloroacetic acid have all been used, and are generally unsuccessful.7
Common warts, flat warts, and genital warts are all caused by different strains of HPV and therefore share many similar therapies. Cryotherapy with liquid nitrogen should be performed with three cycles of at least 10-second freeze followed by complete thaw. A blister should form within 24 hours. This treatment should be repeated approximately three weeks later. Often, for extensive local disease, podophyllin can be also be used. Imiquimod has been shown to be effective in clearing clinical disease as well. HIV-positive individuals usually are infected by more than one HPV-type simultaneously and frequently harbor one of the oncogenic types, which places them at higher risk for anal dysplasia and anal carcinoma. If a patient has a history of perianal warts, receptive anal intercourse, or penile or vaginal warts or reports a partner with penile warts, a Pap smear should be obtained from the anal canal. If any degree of dysplasia is observed, an anoscopic examination with biopsy of suspicious lesions is recommended. In the hospice setting, however, more relevant issues are keeping the lesions at a size that will allow adequate bowel movements without discomfort and also monitoring for secondary bacterial infection of the vegetating mass. Large and potentially obstructive anal lesions must be dealt with surgically. Adequate hygiene, including washing the perianal area after bowel movements instead of wiping it with dry paper, helps prevent secondary bacterial infections.
Fungal infection is no more common in AIDS patients than in the general population, but the character of the infection changes as patients become more immunocompromised. These most common fungal infections are the “tineas,” caused by dermatophyte fungi, followed by Candida infections. As the disease progresses, patients are more susceptible to acquiring deep fungal infections such as blastomycosis and sporotricosis and also to developing cutaneous lesions of generalized systemic fungal infections, such as cryptococcosis and histoplasmosis. There is also a poorer response to standard therapies and higher recurrence rates. Additionally, the resulting skin breakdown may also predispose these patients to bacterial superinfection and bacteremia, which they are ill equipped to handle.
Superficial fungal infections in AIDS patients may be extensive, especially in the groin and feet. Tinea pedis (“Athlete’s foot”), tinea cruris (“jock itch”), and tinea corporis (“ringworm”) all occur with a similar frequency in the general population, but tinea pedis is the most common dermatophytosis seen in AIDS.8 With all three infections, the lesions may become more widespread, larger, and more resistant to traditional therapies. They may also present with atypical clinical features resembling other noninfectious dermatologic problems (Color Plate 9-8).
Oral candidiasis, or thrush, occurs in almost all HIV patients and is often difficult to cure. In addition to immunosuppression, complicating factors include a high rate of oral carriage in even healthy patients as well as frequent and long-term antibiotic use. Classically, there are white plaques on the palate, tongue, and gingival area, which can be scraped off to leave an erythematous, often slightly bleeding base. In the case of long-standing infection, it may be difficult to scrape them off. Dysphagia and sore throat are all commonly associated complaints. Candida intertrigo occurs commonly in patients with warm, macerated, moist skin and very commonly in AIDS patients (covered in Skin Problems in the Chronic, Bedridden Patient on page 198). Candida paronychia is a frequently misdiagnosed condition that is often seen in patients who wash their hands frequently, do dishes frequently, or have their hands in cleaning solutions. Periungual erythema, swelling, and the extrusion of pus is a common presentation, and is often misdiagnosed as bacterial infection. Here, the patient’s history should guide diagnostic and treatment options.
Presentation varies from fungating nodules and tumors to ulcers and diffuse papulonodular disease. Cryptococcosis and histoplasmosis, when affecting the skin, may present with multiple, widespread, translucent, dome-shaped papules with a slight central dimple resembling molluscum contagiosum, but the morphologic variation can be broad.
Tinea can have atypical presentations in these patients, often resembling one of the eczemas or even psoriasis. As a rule of thumb, every lesion that is scaly has to be scraped for a KOH prep. When scraping suspected lesions, use a disposable scalpel blade, held perpendicularly to the skin, collecting the obtained scales on a microscope slide. Then add a drop of 10% KOH, cover with a coverslip, and warm the slide up by placing it under a flame for three to five seconds. The slide is then examined under the microscope looking for the presence of septated, branching hyphae. The highest yield is obtained when the peripheral scales on the edge of the advancing lesional border are scraped.
Although the differential diagnosis for white plaques in the mouth is extensive, thrush is largely a clinical diagnosis. A KOH prep may be helpful when clinical presentation is atypical. Most AIDS patients will have asymptomatic colonization, so the only use of cultures is for speciation and to determine sensitivity. Adherent white plaques on the sides of the tongue in AIDS patients may represent oral hairy leukoplakia, caused by Epstein- Barr virus infection. Biopsy can definitively differentiate the former from squamous cell carcinoma.
Culture is indicated for deep fungal infection. If cryptococcal infection is suspected, India ink stain or Wrights stain may be performed. Culture of histoplasmosis takes several weeks to grow.
For limited disease, topical antifungal preparations should be tried first. Treatment has to be performed for a period of two to three weeks, even after symptoms have completely subsided. Oral antifungal agents are needed when fungal infection is widespread, when it affects a hairy area such as the scalp or beard, or when nails are affected. Currently available oral drugs are griseofulvin, fluconazole, ketoconazole, itraconazole, and terbinafine. Things to keep in mind when selecting an oral antifungal agent are the potential drug interactions with antiretroviral drugs and also with the drugs that are metabolized by the cytochrome P450 system. Many of the oral antifungal agents are associated with a significant risk of hepatotoxicity when given for a prolonged period of time, such as that required for treatment of nail infections. Therefore, in patients with a history of hepatitis or other liver disease, the options are limited. Ketoconazole’s absorption is reduced by achlorhydria that is often seen with AIDS, so it should be taken with a cola soft drink, which can increase absorption by 50%.
In our experience, clotrimizole troches are superior to nystatin swish-andswallow, likely because of greater contact time with the oral mucosa. For difficult to treat infections, studies have shown that PO fluconazole is equal in efficacy to itraconazole.9 The practitioner should keep in mind that even with the best current therapies, Candida albicans relapse rate is high, and the failure rate is even higher. There is a high incidence of resistant Candida species among patients with HIV, and prolonged treatment failures necessitate culture for sensitivity profiling.
Cryptococcal infection is the most common lethal mycosis in AIDS and should be treated with amphotericin B with fluconazole as secondary prophylaxis.10 Histoplasmosis should also be treated with amphotericin 0.5 mg/kg/d IV or itraconazole 200 mg PO bid.
Infestation with the mite Sarcoptes scabeii var hominis results in an intensely pruritic eruption in both the normal host and in the AIDS patient. An investigation for scabetic infestation should always be performed in any patient with a persistent or widespread, pruritic eruption. Keep in mind, however, that there may be significant differences in the clinical presentation of scabies in the immunocompromised host.
Multiple small, pinpoint to pinhead sized erythematous papules that can be intact, but usually are excoriated due to the intense pruritus. Areas commonly affected are the interdigital spaces of the hands, wrists, antecubital fossae, anterior axillary areas, inframammary folds, periumbilical area, waistline, buttocks, and inner thighs. The male genitalia is usually affected and nodules can be seen on the scrotum. The diagnostic clinical finding is the presence of burrows on the skin. They present as a pink papule at the end of a small linear tract only a few millimeters in length, often in the interdigital spaces of the hand or lateral aspects of the feet. In many cases, the papular lesions are caused by an immune response to the mites and, even when they are small in numbers, the affected individuals may still present with widespread skin lesions.
The incidence of this variant is very low in comparison with typical scabies, but higher in AIDS patients than in the healthy population. Varying degrees of hyperkeratotic plaques associated with skin thickening and crusting is observed (Color Plate 9-9). Fissuring is common, as is bacterial superinfection and even bacteremia. Burrows may not be evident because of the thick overlying crust. These patients are infested with millions of mites, and pruritus, if present, is often only minimal. This form of scabies is usually misdiagnosed and, because it is an extremely contagious process, it becomes a walking source of infestation for the health care workers and other patients for prolonged periods of time before patients are correctly diagnosed and adequately treated. It should be noted that there have been no reported cases of HIV transmission via scabetic mites passed from patient to health care worker.
Classical scabies: Insect bite reactions, papular urticaria, drug reaction, folliculitis, prurigo simplex, organic causes of pruritus; crusted scabies: psoriasis, various forms of eczema and lichen planus.
Identification of the mites, their eggs, or their feces from skin scrapings is necessary for diagnosis. The region most fruitful for scraping is a nonexcoriated papule, especially in the burrows. Scrapings can also be performed from under the fingernails because this is a protected area. Once an adequate sample is scraped onto a microscope slide, a drop of mineral oil is placed on the specimen and covered with a coverslip before viewing under the microscope.
Scabetic infestation represents a good example of why topical steroids should not be given to patients until an exact diagnosis has been reached. Suppression of the local immune response around the infection will only help the mite, not the patient. Even though the estimated life span of the mite outside of human hosts is very short, it is important that the patient’s environment, including bed sheets, towels, and personal clothing that have been worn and are not freshly laundered should all be washed. Whenever possible, carpeting and upholstery should be cleaned. This should be done after the patient has completed the recommended treatment. In addition, all intimate contacts and nonintimate household or roommate contacts should be treated simultaneously. Health care workers who had direct skin contact with the patient or their bed should also be treated as soon as possible. Topical antiscabetic preparations include permethrin 5%, crotamiton 10%, and lindane 1%, applied to cover the entire body surface once, washed off 10 to 12 hours later and repeated 10 to 14 days later when the female mite’s eggs hatch. Ivermectin, although not FDA-approved for this purpose, has shown to be effective as a single-dose oral treatment for scabies in both HIV-positive and HIV-negative individuals.11 The dose is 200 micrograms (µg) per kilogram of body weight once and repeated 10 days later if necessary. This is a good option when compliance is questionable and in epidemics affecting hospitals and hospices. Case reports have noted that for the thick plaques of crusted scabies, a combination of oral and topical antiscabetic regimens is likely most effective. For cases of crusted scabies, a keratolytic agent such as salicylic acid 3–5% or urea 20% should also be used to facilitate removal of the crusts that harbor thousands of mites and penetration of the antiscabetic medication. Side effects of ivermectin include eosinophilia and constitutional symptoms. It should not be given to young children, pregnant women, or breastfeeding mothers.
Kaposi’s sarcoma (KS) is the most common tumor seen in patients infected with HIV and is an AIDS-defining illness. More common in homosexual or bisexual men, KS is also 300 times more common in AIDS patients than in patients immunosuppressed for transplants. The etiology is clearly multifactorial; however, there have been significant strides made in the past decade in understanding the pathogenesis of this tumor. At the heart of the pathology is angiogenesis, and various mechanisms are known to be responsible, namely sexual transmission of human herpesvirus 8 (HHV8), an altered cytokine environment and the HIV trans-activating protein, Tat.12 It is thought that in the presence of a dysregulated cytokine milieu, Tat induces HHV8, which also encodes on its genome, viral IL-6. This IL-6 leads to increased expression of endothelial growth factor which, in turn, promotes angiogenesis. 13, 14
The skin is the most commonly affected organ, where this disorder may present with either a few localized lesions or diffusely (Color Plate 9-10). Any body area may be involved with red or purple, hyperpigmented, indurated patches, papules, nodules, plaques, or tumors, but there appears to be a higher predilection for the lower extremities. The lesions tend to be oval shaped, be symmetrically distributed, and to follow skin tension lines. In the oral cavity, the palate and gingiva are usually involved. Chronic lesions may show superficial changes such as scaling and crusting and they may even ulcerate.
Bacillary angiomatosis, pyogenic granulomas, traumatic ecchymoses and hematomas, cutaneous B-cell lymphoma, angiosarcoma. If the clinical diagnosis is in question, simple punch biopsy of the lesion should be diagnostic.
Options for treatment vary according to the extent of the disease, rate of progression, the development of new lesions, and presence of systemic involvement. Therapeutic options for localized cutaneous disease are very different from widespread, symptomatic, systemic involvement (reviewed in Dezube, 2000 15). Local disease can be treated by any number of modalities, including cryotherapy with liquid nitrogen, CO2 laser ablation, infrared photocoagulation, intralesional chemotherapy, surgical excision, electrofulguration, radiation therapy, and alitretinoin 0.1% gel applied topically.
Chemotherapeutic options include paclitaxel or the liposomal anthracyclines doxorubicin and daunorubicin. These modalities are useful for disseminated, symptomatic KS. Paclitaxel is very effective but has a higher incidence of myelosuppression, alopecia, and arthralgias than the liposomal anthracyclines, which are widely considered first-line chemotherapeutic agents in these patients. Radiation therapy is also very effective for palliation in advanced, symptomatic, and extensive disease. A radiation schedule of 3.5Gy/fraction at 3 fractions per week for a total cumulative dose of 21 Gy has shown to reduce visible tumor burden as soon as 2 weeks after completion of therapy.
The importance of successful antiretroviral therapy cannot be overstated. Studies have shown that HAART dramatically reduces the incidence of new KS lesions and can decrease the size of or even clear existing lesions.16
AIDS patients are at high risk for the development of adverse drug reactions because of the sheer number of medications they require as well as their body’s dramatically altered immunologic milieu. The most critical knowledge for the health care worker caring for these patients is the ability to differentiate between drug reactions that are serious and even life-threatening and those that may be tolerated in order to continue a necessary medication.
It has been widely recognized since the early 1980s that patients with AIDS suffer from an increased incidence of cutaneous eruptions directly attributable to trimethoprimsulfamethoxazole17 and that the incidence of drug eruptions from all sources was likely to be approximately ten times higher than in the general population.18
Unfortunately, the cutaneous manifestations of adverse drug reaction are manifold. While a morbilliform eruption with widespread erythematous macules and overlying papules is one of the more common manifestations, urticaria, bullous eruptions, pityriasis rosea-like lesions, palpable purpura, erythema multiforme, and others are also not rare.
The goal is to be able to differentiate between a primary cutaneous process in an ill patient and a drug-related cutaneous reaction. Here, the timing of the medication with the development of rash is critical because most eruptions begin 7-12 days after initiation of therapy. For unfamiliar lesions, a biopsy is always the safest route, making sure an analysis by direct immunofluorescence for immunoglobulin or complement deposition in the skin is performed. This is especially important in the bullous eruptions or eruptions suggestive of vasculitis.
Table 9-3 enumerates the most important indications for discontinuing a medication because of an adverse cutaneous reaction.
Apart from discontinuing medications, lesions of erythema multiforme that are causing significant discomfort may be treated with systemic corticosteroids. It should be noted that their use does not prevent progression to the more severe toxic epidermal necrolysis. Systemic corticosteroid use in toxic epidermal necrolysis is contraindicated and in Stevens-Johnson syndrome is debated. Intravenous immunoglobulin has been reported on a caseby-case basis to be successful in treating the more severe cutaneous drug eruptions, including toxic epidermal necrolysis.19 However, to date there have been no controlled trials to prove its efficacy. If the offending medication is absolutely necessary, desensitization may be performed in cases of non-life-threatening adverse reactions.20
Immobilization during the latter stages of AIDS, especially when in the hospice environment, generates by itself a number of potentially chronic skin disorders. These often chronically bedridden patients, who lack any immune function, suffer from not only skin breakdown and infection, but also from disorders uniquely associated with increased body temperature as well as increased sweating and impedance of the normal sweating mechanisms. The following section deals with the diagnosis and management of intertriginous infections, and with miliaria and Grover’s disease, which are often seen in such patients.
Intertrigo is a general term that describes inflammation and/or infection of the intertriginous areas, specifically the perineum, inframammary region, axillae, and redundant skin folds in obese individuals. Three major infections—dermatophyte or tinea infections, Candida infections, and erythrasma, which is caused by Corynebacteria—all thrive in the warm, moist areas of the intertriginous spaces and are seen in both the healthy and the AIDS populations.
Tinea infections classically present with erythematous patches showing a more active, slightly elevated, scaling border as the fungus advances at the outer edges. The border is frequently scalloped and well defined. The scrotum is hardly ever involved in tinea infections. This is in contrast to Candida infections, which are generally more moist, weepy, and erythematous, with the characteristic satellite lesions at the periphery of the large patch. Erythrasma is much less common than the above but is important to recognize because of its clinical similarity and because, as a bacterial infection, will not respond to antifungal agents. It usually presents as an erythematous/brownish intertriginous patch that has a characteristic coral red fluorescence under Woods lamp. Prompt attention to these conditions is important because inflammation and the frequent maceration seen predispose these patients to skin breakdown and superinfection with bacterial pathogens.
In addition to the overt infectious processes from dermatophytes, Candida, and Corynebacterium, other mimicking conditions may also flourish in the perineal region. Although psoriasis typically affects the extensor surfaces (i.e., knees, elbows) inverse psoriasis often appears in intertriginous spaces. Again with an erythematous, well-demarcated patch with heavy silvery scale, inverse psoriasis may resemble infectious intertrigo. When a friable bleeding base is revealed from gentle removal of scales, this condition should be considered. Additionally, as AIDS progresses, seborrheic dermatitis often becomes more widespread and not uncommonly involves the perineum. Greasy yellow scale on an illdefined, erythematous base differentiates this condition from inverse psoriasis and infectious intertrigo. Finally, irritant contact dermatitis is a very common problem in the hospice setting. As patients approach terminal illness, incontinence and/or chronic diarrhea is very prevalent. This causes tremendous irritation, not dissimilar to diaper dermatitis of infants, accelerating the formation of decubitus ulcers and enhancing bacterial superinfection.
The treatment of dermatophyte and Candida infections is covered in Other Common Infections. The treatment for erythrasma is with topical erythromycin and antibacterial soaps, including benzoyl peroxide washes. In general, it is critical to reduce maceration and predisposing conditions. Appropriate skin care includes washing the affected areas daily or twice daily followed by the use of drying agents such as aluminum acetate or diluted acetic acid soaks and lotions. Hydrophobic barrier creams and ointments such as petroleum jelly or dymethicone- or silicone-containing creams can also be used to prevent recurrence of the problem. One therapy often used for uncomplicated diaper dermatitis is a compound made of 15 g of nystatin cream, 15 g of 2.5% hydrocortisone cream compounded in a zinc oxide base. Zinc oxide helps to dry the area, nystatin reduces yeast colonization, and the steroid reduces inflammation.
Miliaria and Grover’s disease are the more common heat-related conditions in bed-ridden patients. Miliaria, or “prickly heat” is a transient condition usually seen in children during the summer months and it is related to obstruction of eccrine sweat gland ducts. Grover’s disease was originally described as a transient vesiculopapular eruption occurring usually in men over 50 years old. Chronic forms are not uncommon.
Miliaria cristalina presents with small, clear superficial vesicles in bedridden patients with increased perspiration and inadequate ventilation from tight or excessive clothing. Miliaria rubra, or prickly heat, is a very pruritic papulovesicular eruption that produces a burning or tingling sensation. It is common in the flexural fossae and intertriginous areas. Grover’s disease is generally limited to the trunk and presents with erythematous 2 to 3 mm papules and vesicles. There is usually mild pruritus. Grover’s disease is associated with increased temperature and sweating.
Miliaria is a self-limiting condition and requires no specific treatment besides reducing immobilization by frequent decubitus changes, and reducing overheating and heat entrapment by avoiding excessive clothing. Grover’s disease, if chronic, can be treated with Class IV topical corticosteroids twice daily. For persistent cases, alternatives include a 6-month course of isotretinoin or PUVA.
The bedridden patient in any hospital or hospice environment is at constant risk for primary skin breakdown. This represents a significant risk in this immunologically debilitated population because open wounds, chronic diarrhea, and warm, moist environments are fertile ground for superinfection. The diagnosis and treatment of decubitus ulcers will be discussed separately. (See Chapter 25: Prevention of Skin Breakdown.)
A careful history and a comprehensive physical examination with review of pertinent medications, medical history, and exposures are all essential to making a rapid diagnosis of the many potential dermatologic conditions that may arise in the AIDS patient. For the immunocompromised patient, it is essential that topical steroids not be given indiscriminately without accurate diagnosis. When in doubt, a simple biopsy and referral to a dermatologist will save the patient critical time spent on topical therapies that, through their ineffectiveness, may only prolong patient suffering.
 Color Plate 9-1. Prurigo nodules Credit: Ciro R Martins, MD  Color Plate 9-2. Eczema craquele with icthyosis Credit: Ciro R Martins, MD  Color Plate 9-3. Nummular eczema Credit: Ciro R Martins, MD  Color Plate 9-4. Atopic dermatitis Credit: Ciro R Martins, MD  Color Plate 9-5. Psoriasis Credit: Ciro R Martins, MD  Color Plate 9-6. Peri-anal herpes simplex virus Credit: Ciro R Martins, MD  Color Plate 9-7. Molluscum Credit: Ciro R Martins, MD  Color Plate 9-8. Tinea corporis Credit: Ciro R Martins, MD  Color Plate 9-9. Crusted scabies Credit: Ciro R Martins, MD  Color Plate 9-10. Diffuse Kaposi’s Sarcoma Credit: Ciro R Martins, MD |
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