A Dermatological Approach to Vitiligo - Essay Example

Vitiligo: A Dermatological Approach Introduction Vitiligo has been in existence for centuries, but it is only with the new advances in medical technology that doctors are able to accurately diagnose and treat this dermatological disorder. For patients living with vitiligo this new information is priceless; unlike many other disorders, vitiligo is virtually impossible to hide and therefore puts the patient at risk of ridicule from people who do not understand. With the constantly growing capability of the medical profession, patients with vitiligo finally have the opportunity for the normal life they deserve. Vitiligo is found in all parts of the world, and although presentation generally occurs between 10 and 30 years of age (The Skin Site, 2008) it is not unusual to see patients develop symptoms earlier or later in life. This disorder can be found in patients of all races, although it is decidedly more noticeable among dark skinned individuals than members of the Caucasian race, particularly those that have limited exposure to sunlight. Pathogenesis A patient’s epidermis is made up of three types of specialized cells. The Langerhans’ cell is the front line of defense for the immune system, keeping bacteria and other foreign invaders from gaining entrance to the bloodstream. The Merkel’s cell is associated with the sense of touch, and is responsible for the skin tumor known as Merkel cell carcinoma (Wikipedia, 2008). The third type of cell found in the epidermis is the melanocyte, and this is the cell that is involved with vitiligo. Patients suffering from this disease do so because the melanocytes in the skin are either damaged or non-existent, having been destroyed for one reason or another. Since the melanocyte, and the melanin that it contains, are responsible for the pigmentation of the skin these patients experience patches of skin that are either completely lacking in pigment or which are considerably less pigmented than the rest of the skin. There are numerous theories surrounding the existence and spread of vitiligo. Since the melanocytes in areas of vitiligo are dead, rather than simply non-functional, researchers have focused their efforts on determining what could cause the death of these otherwise hardy cells. Their research has determined that vitiligo is not the “cut and dried” disease that it first appears to be. There are multiple forms of the disorder, and numerous subtypes among these forms. While it is less common than other forms of vitiligo, it has been determined that vitiligo can accompany an injury, particularly one which caused severe damage to both the upper and subcutaneous layers of the epidermis. This is most commonly seen with cuts and burns (including sunburn), and the hair that grows in these areas (if, indeed, there is any) is often lacking in pigmentation as well. (National Skin Center, 2008) The pathogenesis in this instance is fairly straightforward; the cell was damaged as a result of the injury and unable to heal, resulting in a patch of vitiligo. While occasionally vitiligo will correct itself, in this instance it is generally a permanent condition. The second type of vitiligo is known as idiopathic, which means that researchers have yet to determine a cause. This is the vitiligo most commonly seen by dermatologists, and that which is the most difficult to treat. There are numerous theories currently being explored to explain the death of these cells in otherwise healthy individuals. Researchers have found distinct links between vitiligo and the immune system, resulting in vitiligo being declared an autoimmune disorder by many physicians. There has also been speculation among the medical community regarding the role that the vast quantity of nerves located in the epidermis, resulting in the skin’s ability to feel, and various toxins and other internal disorders play in the development of vitiligo. Autoimmunity is currently the accepted cause for vitiligo. This theory is supported by the fact that individuals with vitiligo statistically suffer from a high incidence of other autoimmune disorders, such as diabetes, thyroid disease, pernicious anemia (a disorder that results in B12 and folic acid deficiency), Addison’s Disease (an endocrine disorder that occurs when the adrenal glands do not produce enough cortisol and/or aldosterone and can result in darkening of the skin (NIH, 2008)) and alopecia areata, which causes bald spots on the scalp. (DermaNet, 2008) The immune system serves as the body’s defense system against foreign invaders, and while the skin is the first line of defense there are numerous cells in the blood that serve to destroy anything that passes through the epidermis. When these cells identify a bacteria, virus or other foreign substance the immune cells destroy it through a process known as the complement cascade to keep it from causing infection. (Stevens, 2003) Unfortunately, the immune system is neither perfect or predictable. Sometimes it will incorrectly identify a harmless substance as dangerous and launch an attack, as is the case with people with allergies. Autoimmunity is a more severe form of this “in which damage to organs or tissues results from the presence of autoantibody or autoreactive cells”. (Stevens, 2003) These autoantibodies destroy the cells that they have improperly determined to be potentially harmful, causing lasting damage with potentially devastating consequences. Most autoimmune disorders require strict monitoring on the part of medical professionals to prevent mortality or permanent disability to the patient. It’s believed that that is what happens in individuals with vitiligo. The body determines that the melanocytes are foreign attackers. The immune system targets the cells, then eliminates them. When these cells die the skin loses its pigmentation. Since autoimmunity results in the buildup of antibodies to a substance this process will repeat itself over and over, killing melanocytes as they develop and preventing the skin from healing itself and causing a chronic condition. Although autoimmunity would explain the otherwise inexplicable destruction of these cells, it does not specifically address why cells in particular areas are targeted more often than others. Vitiligo is most often found in the face, groin, neck, nipples, ear creases and other body folds, such as the armpits, surrounding halo naevi (pigmented moles) and the hands. (DermaNet, 2008) The inability to determine why these areas are targeted most often, and why vitiligo tends to be a slow-progressing, localized condition, has led researchers to look further into the possibility that autoimmunity may be only a small part of the pathogenesis of this disease. To that end, researchers have begun exploring the theory that vitiligo may be caused by damaged nerve endings found in the upper layer of the epidermis. These damaged nerves result in the death of the surrounding cells, causing a localized vitiligo. (DermaNet, 2008)This theory explains why vitiligo is usually not a systemic disorder; since no autoantibodies are created there is not a systemic destruction of the melanocytes. A study done by the Department of Dermatology at Royal Hallamshire Hospital and the Department of Biomedical Science at the University of Sheffield determined that the nerves in areas affected by vitiligo showed numerous ultrastructural changes. The basement membrane of the Schwann cells, which form the myelin sheath on the axons in the peripheral nervous system, was significantly thicker in lesioned areas than in undamaged areas of the body. Almost half of the abnormal dermal nerves showed minor axonal damage, although the increased mitochondria and rough endoplasmic reticulum found indicated that the body was attempting regeneration. (Al’Abadie, 1995) The results of this study support the fact that there is a neuronal component involved in the development of vitiligo; whether it exists as a separate entity or in conjunction with other factors has yet to be determined. Very few autoimmune disorders will correct themselves, because once the body’s antibodies have identified a substance as an intruder they will readily attack it for the rest of the individual’s life. Nerve endings, on the other hand, have been known to heal themselves. This is why so many people will be able to regain use of a limb after they have been injured. On the other hand, permanent nerve damage can also occur. This presents a serious case for the fact that many times vitiligo is a permanent condition. Alongside possible autoimmune and neural components is the question of the role played by genetics in the onset of vitiligo. A study done in Bangalore, India showed that among populations where intermarriage among families is common there was an increased incidence of vitiligo, with approximately twenty percent of the population developing the depigmented lesions throughout their lifetime.(Huggins, 2005) Those individuals with a family history of vitiligo displayed symptoms much earlier in life than their counterparts. In the instance of this study a genetic model was made that suggested that vitiligo can be passed on as both a dominate and a recessive trait. Individuals with dominant genotypes were among those who presented with clinical symptoms in their late childhood, while those patients who possessed a recessive genotype tended to present with symptoms later in life or following exposure to specific environmental triggers. Further inquiry into the genetic predisposition of vitiligo led to an astonishing discovery by scientists performing a study at St George's, University of London, the University of Colorado at Denver and Health Sciences Center (UCDHSC) and the Barbara Davis Center for Childhood Diabetes. (Spritz, 2007) Researchers in this study began by focusing their efforts on families that showed multiple incidences of vitiligo. The patients targeted showed increased instance of other autoimmune disorders, prompting the researchers to do a full genetic study. They discovered that many of these individuals suffered from a mutation in the NALP1 gene. NALP1 is one of the genes responsible for the operations of the body’s innate immune system, the first line of defense against infection. ““When we are attacked by viruses or bacteria, the innate immune system stimulates the inflammatory pathways and calls the rest of the immune system to action. NALP1 is probably a receptor for bacterial or viral signals.” (Spritz, 2007) NALP1, located on the 17th chromosome, has not been previously implicated in any study of autoimmune disease; however, the fact that these mutations can be handed down from parent to child presents researchers with a fresh outlook on the genetic foundation of vitiligo. If researchers are able to properly identify the gene responsible patients suffering from chronic vitiligo may one day have the option of gene therapy to treat their previously untreatable disease. Clinical Presentation The clinical presentation of vitiligo is fairly straightforward. The lack of melanin will result in unpigmented patches developing on the skin. Individuals with dark skin will likely notice this condition as soon as it begins to appear, particularly if presentation occurs in a highly visible area. Patients with fair skin may not notice until summertime, when their skin fails to tan following exposure to UV rays. Vitiligo lesions are flat and smooth with a darker, well defined border, serving to distinguish them from other dermatological conditions such as tinea versicular (a fungal infestation) that cause the skin to take on a similar appearance. It may, however, be covered by a fine layer of dead skin known as scurf. Scurf on a patch of vitiligo closely resembles the dandruff found on the scalp, and while it may be unattractive it causes no harm. There are two widely recognized forms of vitiligo lesions, segmental and non-segmental. Segmental vitiligo is characterized by an early onset and rapid spread across the body. If these lesions are untreated they will persist throughout the course of the patient’s lifetime; however, spread typically stops within two years after initial presentation. (Huggins, 2006) Segmental lesions show a tendency to stay on one side of the body, as opposed to the mirror imaging commonly seen in non-segmental vitiligo. Non-segmental vitiligo presents with symmetrical distribution of lesions on both sides of the body, and unlike segmental lesions they may continue to present throughout the course of the patient’s lifetime. Occasionally, non-segmental vitiligo will be so extensive that only a few patches of normally pigmented skin remain. This is a condition known as vitiligo universalis. There is also a non-segmental subtype known as focal vitiligo, in which lesions are limited in quantity and have a non-dermatomal distribution. Focal vitiligo may develop into generalized vitiligo or it may stabilize early on. The third subtype of non-segmental vitiligo is known as acrofacial. Acrofacial vitiligo is confined to the skin on the hands, feet and face, and is often seen at the onset of the disease. Like focal vitiligo, acrofacial vitiligo may become generalized as the disease progresses. Vitiligo can present many ways and on many parts of the body. The most typical presentation is shown below, with initial lesions developing on the hands, feet and folds of the body. The lesion is clearly defined and while there may be several patches of vitiligo in close proximity to each other the skin surrounding each lesion shows normal pigmentation. The area lacking melanin is flat rather than raised, preventing it from being confused with other forms of dermatitis. http://dermnetnz.org/colour/vitiligo.html http://en.wikipedia.org/wiki/Vitiligo http://www.skinsite.com/info_vitiligo.htm There are numerous ways in which vitiligo may present. The lesions may be amelanotic, meaning that there is no pigmentation whatsoever, or trichromatic, in which instance the skin is hypopigmented but still retains some of its color. Quadachromatic lesions develop when repigmentation occurs, causing the skin to develop a hyperpigmented band, and macules developing at sites of post-inflammatory hypermelanosis cause the patient to develop what is known as “blue vitiligo”. (Huggins, 2006) Vitiligo is a disease of progression; whether that progression is rapid or gradual depends upon the specific type and subtype, genetic predisposition and contributing environmental factors. Initial presentation of symptoms usually occurs when a small area of the epidermis loses its pigmentation. This loss may be complete, causing the skin to become amelanotic, or partial, causing a trichrome lesion. If the lesion is trichromatic it may continue to lose its pigment; however, this is not guaranteed. A patient may have multiple colors of lesions across the expanse of their body. There are numerous other, less common presentations of vitiligo in other areas of the body. Shown below is an example of mucosal vitiligo. In this case it only affected the mucus glands of the face, focusing around the nose and mouth. http://dermnetnz.org/colour/vitiligo.html In the case of this patient the vitiligo presents only around the eyelids. This type of vitiligo is barely noticeable in light skinned patients, although those with a darker complexion may encounter greater difficulties. http://dermnetnz.org/colour/vitiligo.html Histopathology Vitiligo is generally diagnosed by a simple visual examination, as the lesions are both unique and easily distinguishable. If the physician is unable to determine whether a lesion is caused by vitiligo or another skin condition, however, they may choose to biopsy a sample of the tissue from the affected area and send it to the lab for a histological study or to perform an on-site examination of the skin using a Wood lamp. When a tissue biopsy is sent to the laboratory it will be examined by a technologist using a melanocyte specific stain, generally hematoxylin-eosin (HE). As frozen tissue sections may not respond well to HE, the tech may also need to use an immunohistochemical stain such as Mel-5. Tissue biopsied from early lesions will show a decreased number of melanocytes under the microscope. That number will decrease to zero in a well-established lesion as the disorder progresses and the remainder of the cells die off. Lesions with a hyperpigmented border will show enlarged melanocytes with elongated dendritic processes in the areas of excessive pigmentation, even if they are missing in the remainder of the tissue. In marginal tissue testing may reveal a lymphohistiocytic infiltrate and focal basal layer vacuolar changes. (Huggins, 2006) In addition to biopsy a dermatologist may order a number of tests to determine whether or not a patient is suffering from vitiligo and, if so, what the underlying cause may be. Patients with vitiligo often display autoantibodies in their blood, something which can be determined in the blood bank portion of any research lab. As vitiligo is often associated with thyroid conditions a TSH level may be ordered as well. The biopsy, however, should be considered the diagnostic tool of choice. Psychological Implications While the patient is undergoing testing it is vitally important that the dermatologist employ proper bedside manner in all interactions. Although vitiligo is not considered to be potentially harmful in the medical community, for the patient seeking treatment the disorder has already had a negative impact on their life. Society sets a large store by a person’s appearance. Beauty plays a large part in an individual’s ability to interact with their peers, find a job or, in many cases, walk down the street without having people step away from them because they are afraid that their condition is communicable. Vitiligo can cause severe damage to an individual’s self esteem, particularly if they happen to be dark skinned, because it is an abnormality they cannot hide. This is particularly true of members of the younger generation, specifically women, who have been taught that if their physical appearance does not coincide with that of their peers they will be ostracized. In a society dominated by eating disorders and false ideals, the potential for harm caused by vitiligo should not be underestimated. When a patient first steps into the office it is essential that the physician remain calm and professional, sympathetic without being overly so. Clinical detachment is essential; the patient needs to feel as though they are not being judged on the basis of their appearance while at the same time understanding that their condition is not an abnormal one. Many patients hesitate to seek medical care for vitiligo because they may fear being stared in the waiting room or being told that there is nothing to be done, so they have wasted their time. Many physicians, on the other hand, take a flippant approach to the treatment of vitiligo. Since vitiligo is unlikely to cause lasting physical harm to the patient they often brush aside their concerns or make them feel as though they are overreacting. This immediately causes resentment between patient and doctor and discourages the patient from receiving further medical treatment or testing. As vitiligo is often associated with other chronic autoimmune conditions this can be fatal to the patient. Numerous resources exist for patients who have been diagnosed with vitiligo. Vitiligo Support International, based out of the United States, is the largest vitiligo organization in the world. Patients can visit their website at www.vitiligosupport.org to interact with other members, learn about their condition and find local support groups that they can meet face to face. The American Vitiligo Research Foundation hosts yearly seminars for patients and distributes newsletters, information and referrals. As with Vitiligo Support International, AVRF hosts a networking site where patients with vitiligo can gather together to discuss their disorder and the effect it has had on their lives. They can be reached through their website at www.avrf.org. The Vitiligo Society operates out of the United Kingdom, providing information and support for patients with vitiligo. They host a number of community events throughout the United Kingdom for patients suffering from vitiligo and have a vast network of resources for children and teenagers living with the disorder. Patients can visit their website at www.vitiligosociety.org.uk. In addition to support groups, patients may benefit from therapy to help them to live with their disease. A traditional therapist with experience in helping patients that are suffering from physical deformities may be best suited to work with the patient suffering from vitiligo. Throughout the course of their sessions the patient and therapist will identify the factors in the patient’s life that are making them uncomfortable as relates to their disease, and the patient will learn basic coping strategies to help them carry themselves with confidence. Treatments Once a definitive diagnosis is made the patient will be able to begin treatment. Treating vitiligo is a difficult proposition for the simple fact that it is often impossible to pinpoint the exact cause of a patient’s condition. Since the cause cannot be located, it is impossible to eliminate it and “cure” the disorder. There are a number of therapies currently employed to help minimize the effects of vitiligo and help the patient preserve their quality of life for as long as possible. Almost all patients suffering from vitiligo will be given a topical therapeutic. Corticosteroids are commonly prescribed, and they have been shown to be moderately effective when used on their own. Melagenine, a topical agent derived from the human placenta, is often used to treat childhood cases of vitiligo and has had a high rate of success. (Huggins, 2006) Recent topical therapies currently being prescribed to patients include calcineurin inhibitors; however, these therapies have brought a very limited amount of success, and only after an extended course of treatment. Calcipotriol has been shown to be much more effective, stimulating melanogenesis “through an unknown mechanism involving melanocyte 1-alpha-25 dihydroxy vitamin D3 receptors.” (Huggins, 2006) Patients undergoing therapy with Calcipotriol have experienced noted to complete repigmentation of the lesioned area. (Huggins, 2006) Vitamin D, a vitamin normally provided by the sun, is available in a topical ointment and may benefit some patients suffering from vitiligo. Tacrolimus ointment, a prescription normally used for the treatment of chronic dermatitis, has been shown to help a small percentage of patients suffering from vitiligo. (SkinSite, 2008) Tacrolimus works by suppressing the immune system. Although it was intended to halt the inflammation process that causes discomfort and swelling in individuals suffering from topical dermatitis, this same suppression may help slow the autoimmune response that causes the spread of vitiligo in patients. There are a number of herbal therapies available for the treatment of vitiligo as well. These remedies are often less expensive than pharmaceutical treatments, although they may be more difficult to obtain. For patients who prefer to avoid chemical therapy herbal treatment may be a viable option. Ginkgo extract, a combination of herbs titled Anti-Vitiligo, Glycyrrhiza glabra, Ficus carica, Foeniculum vulgare, Adiantum capillus-veneris, Althaea officinalis, Malva sylvastris, Rosa damascene, Vitis vinfera, Apium graneolens, Zingerbeer officinale, cassia angus tifolia and Operculina turpethum are all currently being marketed as wholistic remedies for patients suffering from vitiligo. Most wholistic remedies carry fewer side effects than pharmaceutical treatments due to the fact that they present fewer foreign elements to the body; however, the wholistic remedies currently being used to treat vitiligo should not be used by patients suffering from digestive disorders. Patients must also take care to watch for allergic response and any sign of irritation in the lesioned or unlesioned areas. Topical therapies, even Calcipotriol, are rarely sufficient to treat vitiligo on their own, and therefore are used in conjunction with phototherapy or surgery. Topical psoralen and UV-A phototherapy are often used to treat nonsegmental vitiligo, restoring the pigment to the effected area. This treatment has only been shown to be effective in about fifty percent of patients, however, and these patients are likely to relapse. It has also been shown to be associated with a number of negative side effects, including (but not limited to) darkening in areas of normal pigmentation, erythema, scaling, pruritus, phototoxic effects, photoallergic reactions, hyperkeratosis of lesional skin and, occasionally, malignancy. (Huggins, 2006) Narrow-band UV-B phototherapy is used to treat patients with generalized vitiligo. This type of therapy has been shown to be effective among sixty three percent of affected patients, and it is highly effective in the treatment of stable vitiligo when over five percent of the body has been affected. The primary appeal of this course of treatment is that the contrast between normal and lesional skin is minimized, allowing the patient to appear more “normal” to the casual observer. The decreased exposure to UV rays and simpler treatment procedure produce fewer side effects, making it more comfortable for the patient. (Huggins, 2006) Targeted phototherapy with the use of an excimer laser is frequently used in patients with localized vitiligo, restoring color to the affected areas without the hyperpigmentation of unlesioned skin seen with PUVA therapy. The laser allows the physician to treat the lesions without exposing the rest of the skin to harmful UV rays, and the results are much more rapid than with other forms of therapy. Although targeted phototherapy is not as effective as its counterparts, the safer administration and rapid results are usually enough to encourage patients to seek this form of treatment. (Huggins, 2006) There are a number of surgical options available for the treatment of vitiligo when other therapies have failed. Autologous skin grafting, in which skin is removed from one section of the body and transplanted at the site of the lesion, has been highly successful in the treatment of segmental vitiligo. Skin grafts have had a positive effect on eighty seven to ninety five percent of patients that have undergone surgery. Skin grafting is not recommended for all patients, however. If the vitiligo is continuing to progress a physician will likely recommend that the patient undergo another form of treatment until the lesions are no longer spreading. Another form of surgical therapy, involving the transplantation of melanocytes, may be used to treat vitiligo in this instance in the hope that the new cells will be able to stop the spread of the disease. (Huggins, 2006) If a patient is suffering from a localized vitiligo and phototherapy has had no effect they may choose instead to visit their local tattoo parlor and tattoo the depigmented lesion. This is considerably less expensive than many of the other treatments available, and unlike phototherapy it is guaranteed to be permanent. Patients should carefully consider the state of their disorder before committing to tattooing, however. The tattooing cannot be undone, which means if the disease continues to spread the patient will be forced to live with the tattoo placed unevenly in a sea of vitiligo, and they will have to decide whether or not to continue tattooing sites as the disorder progresses. Patients suffering from vitiligo universalis may find that all of these treatment options are impractical for them. The cost, extensive side effects and limited chance of success are enough to encourage these patients to turn away from phototherapy or surgery. Instead of attempting to restore the pigmentation to the affected areas they may choose instead to remove the pigment from their unaffected skin by using a bleaching agent. This option may be especially attractive to patients with a naturally dark complexion, as a partial restoration of pigmentation from ineffective therapy will be more noticeable to them than their fair skinned counterparts. There are a number of commercial bleaching agents available for the purpose of evening out skin tone in patients with vitiligo. Most of them utilize a monobenzyl ether of hydroquinone and 4-methoxy-phenol, although a Q-switched alexandrite was recently used to treat a woman with recalcitrant repigmentation successfully. (Huggins, 2006) In addition to topical therapies, it is recommended that patients with vitiligo take a B-complex multivitamin on a daily basis, as well as supplemental folic acid, Vitamin E and ascorbic acid. (SkinSite, 2008) Regardless of the type of therapy they choose to undergo, patients with vitiligo will have to take some extra precautions due to their decreased quantity of melanocytes. Most patients, regardless of how fair their skin, will have some protection from the sun in the form of the melanin in their cells. Since patients with vitiligo do not have this front line of defense they will by necessity have to take extra care to protect their skin from sunburn. Exposure to the sun should be limited, and the lesioned areas carefully covered with clothing and sunscreen when the patient is out of doors. Despite their high rate of success, there is no guaranteed treatment for vitiligo. Until researchers are able to accurately pinpoint a specific cause for this disorder it will continue to affect thousands of people around the world; however, advances in medical technologies have brought researchers closer than ever before. There is no doubt that if scientists continue to make advances in the field of dermatology the day will come when patients with vitiligo will be able to enjoy the quality of life that they deserve. Read More