Clinical Dermatology

>масиmin A deficiency results in the development of hyperkeratosis and scaling skin lesions. Not surprisingly, this observation has led many clinicians to treat various types of keratinizing disorders with vitamin A. Some beneficial effects were noted, but vitamin A toxicity often supervened before adequate therapy had been accomplished. This led to a search for safer variants of the vitamin A molecule. The first clinically successful retinoid was the trans form of retinoic acid (Tretinoin, Retin-A), which, when topically applied to the face in acne patients, results in loosening and dissolution of the follicular plugs responsible for the initiation of acne lesions. Considerable unwanted inflammation occurs concomitantly with this keratolytic effect, but in spite of this drawback, topically applied transretinoic acid remains a first-line medication in the treatment of acne. Recently, several studies have demonstrated that topically applied tretinoin can, at least to a modest degree, reverse the cutaneous effects of photoaging.

Two retinoids, the cis form of retinoic acid (Isotretinoin, Accutane) and the aromatic retinoid (Etretinate, Tegison), are available for oral use in the United States. The former has shown remarkably good results in the treatment of acne, and both produce considerable improvement in some of the papulosquamous diseases such as psoriasis, lichen planus, pityriasis rubra pilaris, Darier’s disease, and ichthyosis. The retinoids also have an antioncogenic effect. Specifically, there is about a 40% response rate in patients with mycosis fungoides and other forms of cutaneous T-cell lymphoma. One can also temporarily delay the appearance of skin tumors in patients with xeroderma pigmentosum and nevoid basal cell carcinoma syndrome.

The dosage of isotretinoin used in acne patients is 0.5 to 1.5 mg/kg. For practical purposes a decision is usually made to use either 40 or 80 mg/ day. The lower dose is associated with£ewer side effects and thus has better patient compliance. Unfortunately, the interval until return of sebaceous gland function and the reappearance of acne is shorter (6 to 18 months) than it is when the larger dose is used. The beneficial effect in acne occurs as a result of dissolution of the follicular plug, reduction in sebaceous gland size and activity, and, possibly, antibacterial and anti-inflammatory effects.

Etretinate (Tegison) is the retinoid usually used for the treatment of psoriasis and other papulosquamous diseases. Usually, dosage is limited to 1.0 mg/kg (75 mg/day) because of the onset of unacceptable side effects above that level. Etretinate has a particularly good effect in pustular psoriasis, but for the other forms, PUV A therapy is sometimes added (RePUV A-retinoids plus PUV A) to obtain an optimal response.

Many toxic effects are associated with the oral use of retinoids. Patients taking isotretinoin for acne regularly develop severe xerosis and cheilitis. Less often, myalgia, arthralgia, conjunctivitis, epistaxis, and hair loss are experienced. Triglyceride levels increase in these patients and must be monitored. Cholesterol levels may also rise, and some disturbance in liver function studies may be noted. Long-term administration is accompanied by idiopathic calcification of the spine in an unknown percentage of patients.

Of greatest importance is the fact that the retinoids are among the most potent teratogens ever used in medicine. Retinoids may not be given until it is certain that a patient is not already pregnant, and pregnancy must then be prevented until 2 months after 13-ci,-retinoic acid is discontinued, The teratogenic risk with isotretinoin cannot be overemphasized; tragic birth defects have been reported all too often through careless prescribing and contraceptive failure. Etretinate, because it remains at detectable levels for years after its use has been stopped, cannot be given to women capable of conceiving.

A wart is a lump on the skin produced when a virus invades skin cells and causes them to multiply rapidly. Some people have a low resistance to the various viruses that can cause warts and are therefore more likely to have them. Wart viruses spread by touch or by contact with the skin shed from a wart.

Warts are common in teenagers, less so in children, and even less so in adults. There are no serious health risks associated with warts, but they can cause embarrassment because of their appearance.

What are the symptoms of Warts?

There are several different types of warts, each produced by a specific virus. The common wart, also called a verruca or a plantar wart, is a small, hard, horny, white or pink lump with a cauliflower-like surface. Inside are small, clotted blood vessels that resemble black splinters. The common wart can grow anywhere on your body but is most likely to develop on your hands. On the bottoms of your feet and palms of your hands, a common wart tends to become pushed in so that its surface is level with the rest of the skin. Several warts may appear next to one another on your foot, forming a mosaic-like area 25 mm (1 in) or more across.

Common warts on most parts of the body are usually painless. However, a wart on the underside of your foot can make you feel quite uncomfortable, as though you are walking with a stone in your shoe.

Among the other types of warts are plane warts, which are small, brown, smooth warts that occur most often on children’s faces .Another type of wart is called molluscum contagiosum. These are tiny, white, pearly lumps, each with a central depression. These are also most common in children. peline warts and vulval warts also occur.

What should be done?

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Most warts disappear naturally, often within a few months but sometimes over several years. You may prefer to wait for this to happen. But if you have any warts that you consider unsightly or annoying, carry out the self-help described below to remove them.

However, there are two cases in which you should consult a physician. One is if you penile or vulval warts. The other is if you develop any sort of wart and you are over the age of 45. In older people, what looks like” wart may be a more serious skin condition. such as skin cancer.

What is the Treatment of warts?

Self-help: There are many folk remedies for removing warts, but their apparent effectiveness is simply due to the fact that most warts eventually disappear of their own accord. The best way to treat unsightly warts is to apply a wart remedy in the form of paint. cream or plaster. These are available without a prescription at most drugstores. These preparations contain chemicals that destroy the abnormal skin cells. However, these chemicals will also damage surrounding healthy cells, so the preparations should always be applied carefully to minimize soreness.

Do not treat warts on your face or genitals with a wart remedy, because the skin on these areas is very sensitive. And never allow these preparations to get into your eyes.

If you have an unsightly or annoying wart that does not respond to this treatment, see your physician.

Professional help: Your physician may prescribe a more effective kind of wart preparation. If this fails, the doctor can remove the wart by freezing it with liquid nitrogen or burning it off with electricity. A few days after this rather painful treatment, the wart will probably fall off. If it does not, repeated treatment should remove it. As an alternative to freezing or burning, a wart can be scraped off (curettage) after first being numbed by a local anesthetic. Occasionally a wart seems to be resistant to all forms of treatment.

Considerable controversy exists regarding the degree to which psychologic factors can adversely affect the skin. But even those who doubt the etiologic effect of psychic disability recognize that the presence of skin disease often results in the development of anxiety or depression. Whether cause or effect, these psychologic factors can often be handled by a simple, common sense approach: warmth, a willingness to listen, and support. When more than this is needed, the clinician must be ready either to treat the patient with psychotropic medication or to offer appropriate referral.

Benzodiazepines such as chlordiazepoxide (Librium), diazepam (Valium), and the shorter acting agent alprazolam (Xanax) are useful adjuncts in the treatment of associated anxiety. They are particularly helpful in the control of pruritus and will often work in situations where antihistamines alone have failed. As in the case with antihistamines, the usefulness of the benzodiazepines, particularly Librium and Valium, is often limited by the side effect of drowsiness. This can be partially circumvented by the administration of chlordiazepoxide (10 to 25 mg) or diazepam (5 to 10 mg) at suppertime and, if necessary, again at bedtime. These medications are particularly helpful in the control of the nighttime scratching that is so characteristically present in patients with atopic dermatitis. They are also worth trying in chronic urticaria unresponsive to conventional antihistamine therapy. Habituation, of course, is a problem of considerable importance. This risk can be lessened by avoiding the use of these agents in people with past drug-dependency problems, by limiting the number of pills prescribed, and by sharp restriction on refills.

Phenothiazines such as chlorpromazine (Thorazine) and trifluoperazine (Stelazine) are at least as effective as the benzodiazepines. They are used less often because of a greater frequency of side effects and because of a widespread belief that they are too potent to be used by clinicians other than psychiatrists. The phenothiazines have a chemical structure that is very close to that of some of the antihistamines. It is possible that the efficacy of both groups of drugs depends on their mixed antihistaminic and tranquilizing effect.

Recently, a new, nonsedating, non habituating anxiolytic agent (buspirone, Buspar) has become available. It differs from the above agents inasmuch as it acts on serotonin receptors rather than on y-aminobutyric acid (GABA) receptors. In my experience it is somewhat less effective than the benzodiazepines, but I use it fairly frequently because of its excellent safety profile. I generally start with a dose of 5 mg b.i.d. and increase to a final dose of 10 mg b.i.d.

Depression is a problem that is overlooked to an even greater degree than anxiety. I believe that it is present in at least 10% to 20% of patients with serious dermatologic disease. Mild depression often improves as the skin disease clears and, of course, requires no specific therapy. Depression of greater severity deserves greater attention. Patients should be offered the opportunity for psychotherapy or medical treatment or both. Endogenous depression is thought to be more amenable to treatment with medication than are other forms of depression, but many clinicians believe that a therapeutic trial is worthwhile regardless of diagnosis.

The tricyclics amitriptyline (Elavil) or doxepin (Sinequan, Adapin) given in a single daily dose at bedtime are used most often. The usual starting dose with either is 25 mg, but this can gradually be increased to 150 mg as necessary. The tricyclics are extraordinarily effective antihistamines and appear to be particularly effective in the treatment of resistan t chronic urticaria. Imipramine (Tofranil) is also effective and may be somewhat less sedating. Both physician and patient need to remember that the maximum effect of these medications is not apparent until they have been taken for 3 weeks. Side effects of drowsiness and confusion are fairly common, but other more serious cardiovascular and CNS side effects are only rarely seen.

Toxicity associated with the use of tricyclics often leads to a low level of patient acceptance. Several other alternative drugs are available and are well worth trying in certain circumstances. Alprazolam (Xanax) has antidepressant effects as well as the anxiolytic effects. Trazodone (Desyrel) is chemically unrelated to the tricyclics and appears to function as a serotonin antagonist. Fluoxetine (Prozac) is another serotonin antagonist that produces very little drowsiness. Recently, some concerns have been raised about its ability to potentiate suicidal ideation, but most doubt that this occurs. I have used it very effectively in a dosage of 20 mg each morning. Clomipramine (Clozaril) may have particularly good effect on obsessive-compulsive disorders such as trichotillomania, but high cost and concerns about safety have kept it from more widespread use.

Topical steroids represent a class of corticosteroids that have been incorporated into lotions, creams, and ointments. Their primary pharmacologic effect is the reduction of inflammation. A secondary antipruritic effect accrues as a result of the decreased inflammation. Topically applied steroids are extremely useful in one group (eczematous diseases), moderately useful in a second (papulosquamous diseases), and somewhat useful in a third (vesiculobullous diseases).

In using topical preparations the clinician must make four decisions: what brand? what strength? what vehicle? and what quantity? lists a few of the most widely sold products. They have been grouped, on the basis of my experience, into rather arbitrary categories of low-potency, mid-potency, and high-potency preparations. A steroid from the low-potency group can be used for all acute and subacute eczematous diseases. A steroid from the mid-potency group can be used for chronic and resistant eczematous diseases and for most papulosquamous diseases. A steroid from the high-potency group can be used for eczematous diseases of the palms and soles and for resistant papulosquamous disease.

A special caveat applies to use of corticosteroids on the face and genitalia. In these two locations, only nonfluorinated, low-potency preparations such as hydrocortisone should be used. To do otherwise leads all too often to the development of a rosacea-like eruption on the face and striae formation on the upper inner thighs.

The choice of a vehicle for topical steroids depends on the distribution and extent of the disease to be treated. As a general rule, creams represent the best choice. Lotions and/or solutions, because of their ease of spreading, can be used in hairy areas. Ointments can be used where additional lubrication is desirable and can be substituted for creams when patients indicate that stinging on application has been a problem. In addition, for a given strength of steroids, ointments are slightly more efficacious than creams. This advantage is based on the fact that the partition coefficients for ointments allow for better transfer of the active ingredient from the vehicle into the lipid layer of the skin.

Most topical steroids come in a small and a large size. Generally, the small size is about 15 g, and the large size is 45 to 60 g. For limited disease, such as that which occurs on the hands and feet, the small size will be sufficient. For larger areas, or where it is anticipated that treatment will be carried out for weeks at a time, the large size will offer better economy.

Patients have generally been instructed to apply topical steroids 3 or 4 times daily. It is, however, becoming increasingly apparent that equally good results can be obtained with as few as one or two applications a day. One of these applications ought to occur directly after bathing, since penetration is slightly better and spreading occurs more easily on well-hydrated skin.

Patients are also usually uncertain how much should be applied and how thinly it ought to be spread. The amount to be applied can be stated in “fingertip units” (FTUs). A FTU is the amount of cream (expressed from the tube as a cylinder) that occupies the space from the skin crease overlying the distal interphalangeal joint to the tip of the finger. Each FTU contains about 0.5 g of cream or ointment. It takes about 1.0 FTU to cover the hand, 2.5 FTUs to cover the face and neck, and 3.5 FTUs to cover the whole arm. Generally, the product should be spread as thinly as possible; it is never necessary to leave an easily visible layer on the skin.

Penetration and thus the clinical efficacy of topically applied steroids can be enhanced by the addition of occlusive techniques. Such occlusion can be obtained through the use of plastic or latex gloves for disease of the hands, Baggies for disease of the feet, wrapped plastic film for disease of the arms or legs, and a vinyl sweat suit for disease of the trunk. In addition, it is possible to use occlusive dressings with adhesive backing (such as Actiderm or Duo-Derm) over small areas of disease. Unfortunately, occlusion, while enhancing efficacy, can lead to local problems, such as atrophy, miliaria, and folliculitis, as well as to systemic problems as a result of greatly enhanced percutaneous absorption.

Long-term use of topical steroids, whether there is occlusion or not, also raises a question about the potential risk of systemic absorption. This is not a significant problem when low-potency steroids such as hydrocortisone are used, even over large body surhlce areas. Mid- and high-potency steroids cause no trouble when used over small areas, but some detrimental effect on the pituitary-adrenal axis can be demonstrated when whole-body application is carried out. As might be expected, extra care should be taken when children are treated, since their large surface area-to-volume ratio increases the effective concentration of whatever amount is absorbed

Itching frequently occurs in association with inflammatory skin diseases and in this setting, it is probably due to the action of inflammatory mediators (such as histamine, prostaglandins, and kinins) on cutaneous nerve endings. The release of proteinases during the process of inflammation may also play an important role. The same nonmyelinated nerves responsible for the transmission of light pain appear to carry these itch impulses to the brain.

Conventional wisdom suggests that all itching is qualitatively the same, but empirical observations suggest that this might not be so. For instance, patients with urticaria often complain extremely severe itching, but only rarely does this pruritus lead to excoriation. On the other hand, patients with dermatitis herpetiformis regularly scratch their lesions even when the pruritus is perceived as only moderately severe in intensity. Moreover, those individuals who are genetically atopic seem predisposed to vigorous excoriation at the slightest provocation, whereas nonatopics rarely scratch uncontrollably. From a practical standpoint, pruritus appears to depend on four major factors: (1) the type of disease-some conditions are inherently more pruritic than others; (2) the environmental condition on the skin-xerotic and sweaty skin favors itching; (3) genetic factors atopics have a lower threshold for itching than do non atopies; and ( 4) the psychologic set of the patients-itching is more severe in anxious and depressed patients. Those diseases that are, to a greater or lesser degree, inherently pruritic are listed, but the severity of pruritus experienced will be at the least partially dependent on other factors.

Fungal elements (hyphae and/or spores) can be found in affected tissues taken from patients with supemcial fungal diseases such as candidiasis, pityriasis (tinea) versicolor, and dermatophyte infections of the skin, hair, and nails. The potassium hydroxide (KOH) preparations that identify these hyphae are both sensitive and specific. Scale, pustules, blister roofs, and clippings taken from hair and nails may be examined with this technique. Most often, KOH examination will be carried out during the evaluation of scaling disorders. In such instances, scrapings are obtained after the affected skin has been moistened with an alcohol sponge or with tap water. Then, before the lesion dries, the sharp edge of a no. 15 scalpel blade held perpendicular to the skin is scraped across the surface. The moistened scale that sticks to the edge of the blade is then transferred to a microscope slide. One drop of a 10% to 20% solution of potassium hydroxide (KOH) is then placed over the material on the slide. A coverslip is added. If the scale is fine and has been spread thinly on the slide, the preparation can be examined immediately. If the scale is thick or if fragments of hair or nails are to be examined, gentle heating of the slide may be necessary in order to get a layer of cells thin enough to examine.

In examining the slide the condenser is racked to its lowest position, and the intensity of the light source is reduced. These two maneuvers increase the contrast between the fungal hyphae and the underlying epithelial cells. The medium-power objective is used for scanning the field, and the high-power objective is used to confirm the presence of suspected hyphae.

In pityriasis (tinea) versicolor, fungal hyphae are short, stubby, and vaguely” Y” shaped . Small round spores are numerous and are collected in clusters around the hyphae. The terms “grapes on a branch” and “spaghetti and meatballs” are often used to describe these hyphae and spores.

In dermatophyte and Candida infections the hyphae are thinner and longer. Few if any spores are present. Most observers cannot easily separate the pseudohyphae of Candida infections from the true hyphae of dermatophyte infections, and a decision as to which of the two infections is present usually depends on the clinical presentation or subsequent culture.

Artifacts are commonly present in KOH preparations and may be confused with hyphae. Cotton threads are thicker and lack parallel sides and branching. Hairs have parallel sides, but they too lack branching. The edges of epithelial cells sometimes overlap and appear to form a continuous, branching line. In such a situation, compression of the coverslip against the slide will cause the cells to change position and separate, thus breaking up the erroneous hyphae-like appearance of the cell outlines.

The unequivocal presence of hyphae on a KOH preparation identifies the disease in question as being of fungal origin. Therapy can be initiated on the basis of this finding without waiting for the report of a fungal culture.

Tremendous advances have been made over the past decade in the field of antiviral therapy. Acyclovir, which was commercially released about 10 years ago, is the therapeutic agent of choice for the treatment of herpes simplex and varicella-zoster infections. Acyclovir itself is not an active antiviral agent. When administered it is converted to the active, phosphorylated form of the drug by the action of virally coded thymidine kinase. The active form interferes with DNA polymerase and in so doing prevents viral replication. Host cells are relatively unaffected because they lack a thymidine kinase that can phosphorylate the parent acyclovir compound. Moreover, human cellular DNA polymerase is more resistant to drug effect than is viral DNA polymerase.

The adult dosage of orally administered acyclovir for the treatment of active herpes simplex infection is 200 mg 5 times/day. It is given for 10 days in primary infection and for 5 days in recurrent infection. For patients with chronic, frequently recurring, oral or genital herpes, the drug may be given continuously in a dosage of 200 mg 2 or 3 times/day. The Food and Drug Administration (FDA) has approved continuous therapy for up to 1 year, but studies have indicated that it can be given safely and effectively for appreciably longer periods of time.

Acyclovir is also effective, at appreciably higher dosage, in the treatment of varicella and herpes zoster (”shingles”). The adult dose for herpes zoster is 5OO mg (an 5OO-mg tablet is available) 5 times/day for 7 to 10 days. Although the symptoms and signs of zoster are ameliorated, acyclovir treatment has not yet been documented as effective in preventing the development of postherpetic neuralgia. Dosages and indications for use are just not being established for patients with varicella.

Side effects rarely occur with the use of orally administered acyclovir in the dosages. Resistance of the herpes viruses to acyclovir occurs with some frequency, but this has not represented a clinical problem, so fur at least, in immunocompetent patients.

Many, maybe most, cases of allergic contact dermatitis cannot clinically be distinguished from other types of eczematous disease. Patch testing is of help in identifying such cases and in confirming clinically suspected cases. However, because of Bayes’ theorem, patch testing (like other diagnostic tests) is of more use in confirming a suspected clinical diagnosis than in indiscriminate screening.

Patch testing can be carried out with a suspected contactant itself (”use test”) or with the chemical constituents of the contactant. The former is usually more practical, since it does not require the purchase and periodic updating of a patch test kit. Use tests are suitable for most nonindustrial contactants such as clothing, cosmetics, and medications where the item in question has been designed for direct application to the skin. Use tests may be considered inappropriate, when evaluating industrial and laboratory chemicals, because of the possible development of an unexpectedly severe reaction.

A use test is performed by taping the suspected contactant tightly against the skin for 48 hours. At the end of 48 hours (or earlier if the patient experiences severe itching) the bandages or tapes are removed, and the site of application is examined. Positive reactions will be red, raised, and pruritic. Flat, red reactions are interpreted as indeterminate and are not ordinarily considered clinically important. Negative reactions, of course, show no visible change at all. Care should be used so that irritant reactions to the tape are not misinterpreted as reactions to the contactant.

Patch test kits are available for more sophisticated types of testing. These kits contain appropriately diluted concentrations of the most commonly encountered contact antigens. They are generally used to screen either for possible contactants in eczematous disease of unknown etiology or for identification of a single, specific antigen in patients with positive use tests. The complexity of this type of testing together with the need to continually replace outdated material makes the use of patch test kits impractical for most generalists.

A positive patch test does not automatically confirm a diagnosis of contact dermatitis any more than a positive tuberculin skin test proves that a patient’s pulmonary disease is due to tuberculosis. Proof that a patient has allergic contact dermatitis requires both the presence of a positive patch test and improvement of the patient’s condition when the suspected contactant is removed from the patient’s environment.

Griseofulvin is an orally administered antibiotic that provides effective treatment for most dermatophyte fungal infections. Absorption of griseofulvin from the gastrointestinal tract is less than ideal, but it can be enhanced when particle size is decreased during the manufacturing process. Two forms of griseofulvin are in current use. The first is called “microsized” and is the form of griseofulvin used when a prescription for the generic product is written. Dosage with this form of griseofulvin is generally 1.0 g/ day, divided into a morning and evening dose taken with meals. The second utilizes an even smaller particle size, which has been suspended in polyethylene glycol (Gris-PEG, Fulvicin PIG). The recommended dosage with these products is 500 to 750 mg/day. Griseofulvin is delivered to the stratum corneum via transepidermal water loss and through the deposition of sweat containing griseohllvin on the surface of the skin. Concentration of the drug in the stratum corneum is thus higher than can be obtained in the plasma.

Systemically administered griseofulvin can be used in all cases of tinea capitis, fungal folliculitis in areas other than the scalp, and onychomycosis; topical antifungal therapy is not etlixtive for these three conditions. Griseofulvin is also useful in instances of tinea corporis that are too extensive for topical therapy. Griseofulvin is not effective in the treatment of cutaneous yeast infections such as candidiasis or pityriasis (tinea) versicolor, nor is it effective in the treatment of systemic hmgal infections.

Griseofulvin has an unjustifiably bad reputation for the frequency and severity with which side effects occur. Gastrointestinal upset and headaches develop in about 10% of patients, but they are usually not severe enough to warrant discontinuation of the medication. Urticaria occurs in 1 % or 2% of patients; this does require discontinuation of use. Photosensitivity eruptions, proteinuria, and leukopenia occur with great rarity. Most clinicians do not obtain urine and blood tests for patients taking griseofulvin for less than 3 months. Griseofulvin is contraindicated in patients with all types of porphyria and should be used with extreme care in patients taking warfarin-like anticoagulants.

Ketoconazole represents a great advance in the treatment of fungal and yeast infections. Advantages include greater efficac)’ in resistant dermatophyte infections, effectiveness against yeast as well as dermatophyte infections, and once daily dosage. Unfort­unately, these are partially olfset by its very high cost, interaction with other medications, potential for significant hepatoxicity, and steroid-like and antiandrogenic properties when taken in high doses. As a result, it probably represents the systemic treatment of choice only for griseofulvin-resistant infections, short-term therapy for pityriasis (tinea) versicolor, some systemic fungal diseases, and unusual cases of onychomycosis.

Ketoconazole obtains its antifungal effect by interfering with the integrity of the fungal cell walls. It is generally given for cutaneous infections in a single morning dose of 200 mg. Rarely, twice that dose will be required. Long-term administration such as would be required for routine nail infections is discouraged because of some remaining concern over toxicity.

Fluconazole (Diflucan) is a new triazole antifungal agent related to ketoconazole. It is currently approved for treatment of severe candidal infections only, but it is also an effective agent for dermatophyte fungal infections. It appears to be appreciably safer than ketoconazole, but this advantage is currently offset by its extremely high price.

Itraconazole is another new triazole that has just been released in the United States. It is extremely effective against dermatophyte infections; its use in onychomycosis results in a cure rate roughly twice that for griseofulvin. It is also effective against sporotrichosis.

Terbinafine is a member of the allylamine family, but unlike naftifine, it is suitable for both topical application and oral administration. It is an extremely effective agent against dermatophytes and appears to be quite safe. Release in United States is expected shortly.

Flucytosine and amphotericin B are antifungal agents that are rarely used by dermatologists. These agents are not discussed here, therefore.