Shingles (Herpes Zoster)
Herpes Zoster, colloquially known as shingles, is the reactivation of varicella zoster virus (one of the Herpesviridae group), leading to a crop of painful blisters over the area of a dermatome. In Italy and in Malta, it is sometimes referred to as “St. Anthony’s fire”. Prior to implementation of the universal varicella vaccination program in the U.S., incidence of shingles increased with advancing age. The incidence rate in children aged less than 10 years was approximately 70 cases/100,000 person-years, increasing to 550 cases/100,000 person-years among adults aged 50 to 59 years. Historically, it was thought that shingles incidence increased due to an age-related decline in immunity; however, recent studies suggest that incidence of shingles is linked to the reduced frequency of periodic exogenous (outside) exposures to children with varicella (chickenpox) due to the increasing vaccination of that population. These exposures produced an immunologic boost that helped suppress the reactivation of shingles. Shingles incidence is high in the elderly (over 60), as well as in any age group of immunocompromised patients. It affects some 1 million people per year in the United States and can involve excruciating pain. Many patients develop a painful condition called postherpetic neuralgia which is often difficult to manage.
Treatment is generally with antiviral drugs such as aciclovir (Zovirax), famciclovir (Famvir) or valaciclovir (Valtrex). For the antiviral drugs to be effective, patients typically need to begin taking them within 2-3 days of the appearance of the rash.
In some patients, herpes zoster can reactivate subclinically with pain in a dermatomal distribution without rash. This condition is known as zoster sine herpete and may be more complicated, affecting multiple levels of the nervous system and causing multiple cranial neuropathies, polyneuritis, myelitis, or aseptic meningitis.
The word herpes comes from the Greek word for snake; it is cognate with herpetology.
Signs and symptoms
The earliest symptoms of shingles include headache, sensitivity to light, flu-like symptoms without fever, as well as itching, tingling, and extreme pain where the rash is developing. Often, pain is the first symptom. This pain can be characterized as stinging, tingling, numbing, or throbbing, and can be pronounced with quick stabs of intensity. Then 1-3 crops of red lesions develop, which gradually turn into small blisters filled with serous fluid. A general feeling of unwellness often occurs. In some cases, the rash does not form blisters, but has an appearance much like urticaria (“hives”).
As long as the blisters have not dried out, HZ patients may transmit the virus to others. This could lead to chickenpox in people (mainly young children) who are not yet immune to this virus. The contagion factor is not high, however, HZ patients may also transmit the virus in the form of shingles to those living in close contact with the patient. Persons with low immunity are particularly susceptible to the HZ virus. In this case, common sense precautions should be used: Do not allow anyone to come into contact with an item of clothing or towel that has been used by the HZ patient. Furthermore, it is always a good idea to cover any open shingle blisters. Although the infection can be passed onto others in the form of shingles, it is more common in the form of chickenpox.
Chickenpox virus can remain dormant for decades, and does so inside the ganglion near the spinal cord. As the virus is reactivated it spreads down peripheral nerve fibers and produces intense pain. The blisters therefore only affect one area of the body and do not cross the midline. They are most common on the torso, but can also appear on the face (where they are potentially hazardous to vision) or other parts of the body.
Outbreaks occur for many different reasons, most of which are a result of events which decrease the immune system such as aging, severe emotional stress, severe illness or long-term use of corticosteroids. There have been recorded cases of outbreaks occurring due to unmanaged stress or other stresses to the skin such as pinching in more sensitive areas of the skin (nipples, ears, and underarms), scratching, or biting.
The diagnosis is visual; very few other diseases mimic herpes zoster, especially in the localization of the rash, which is otherwise quite similar in appearance and initial effect to that of poison oak or poison ivy. In case of doubt, herpes tests can be performed where fluid from a blister may be taken so the cells can be analyzed in a medical laboratory. Herpes test are among many possible forms of testing for the disease. Physicians can take a viral culture of the skin, which involves a microscopic examination of the skin using a Tzanck preparation. While looking at the cell obtained from the blister, the cells infected with the herpes virus will appear very large and contain many dark nuclei. By taking a complete blood count there may be an elevated number of white blood cells, which is an indirect sign of infection. There may also be a rise in the antibody to the virus that will give indication of the virus’ reactivation as well. Lab tests are necessary because, depending on the affected sensory nerve, the pain that is experienced before the onset of the rash may be misdiagnosed as pleurisy, myocardial infarction, appendicitis, cholelithiasis, or a migraine headache.
|The causative agent for herpes zoster is varicella zoster virus (VZV). Most people are infected with this virus as a child, as it causes chickenpox. The body eliminates the virus from the system, but it remains dormant in the ganglia adjacent to the spinal cord (called the dorsal root ganglion) or the ganglion semilunare (ganglion Gasseri) in the cranial base.Generally, the immune system suppresses reactivation of the virus. In the elderly, whose immune response generally tends to deteriorate, as well as in those patients whose immune system is being suppressed, this process fails. (Some researchers speculate that sunburn and other, unrelated stresses that can affect the immune system may also lead to viral reactivation.) The virus starts replicating in the nerve cells, and newly formed viruses are carried down the axons to the area of skin served by that ganglion (a dermatome). Here, the virus causes local inflammation in the skin, with the formation of blisters. The pain characteristic of herpes zoster is thought to be due to irritation of the sensory nerve fibers in which the virus reproduces.|
Acyclovir (an antiviral drug) inhibits replication of the viral DNA, and is used both as prophylaxis (e.g., in patients with AIDS) and as therapy for herpes zoster. Other antivirals are valacyclovir and famciclovir. Steroids are often given in severe cases. During the acute phase oral acyclovir should be given five times daily for 7 to 10 days. Immunocompromised patients may respond best to intravenous acyclovir. In patients who are at high risk for recurrences, an oral dose of acyclovir, taken twice daily, is usually effective. Use of acylovir is most effective in moderating the progress of the symptoms if taken as early as possible, so medical care should be obtained as soon as the condition is recognized. It is also reported that the amino acid lysine inhibits the replication of herpes zoster.
The long term complication postherpetic neuralgia may cause persistent pain that lasts for years. Pain management is difficult as conventional analgesics may be ineffective. Alternative agents are often used, including tricyclic antidepressants (particularly amitriptyline), anticonvulsants (e.g. gabapentin), and/or topical capsaicin.
Zostavax is a vaccine developed by Merck & Co. which has proven successful in preventing half the cases of herpes zoster in a study of 38,000 people who received the vaccine. The vaccine also reduced by two-thirds the number of cases of postherpetic neuralgia. However, prior to the vaccine, it has long been known that adults received natural immune boosting from contact with children infected with varicella. This helped to suppress the reactivation of herpes zoster. In Massachusetts, herpes zoster incidence increased 90%, from 2.77/1000 to 5.25/1000 in the period of increasing varicella vaccination 1999-2003. The effectiveness of the varicella vaccine itself is dependent on this exogenous (outside) boosting mechanism. Thus, as natural cases of varicella decline, so has the effectiveness of the vaccine.
Often the same treatment given to burn victims relieves the pain of shingles, including over-the-counter moist burn pads.
The rash and pain usually subside within 3 to 5 weeks. The most common chronic complication of herpes zoster is postherpetic neuralgia. Pain that persists for longer than one to three months after resolution of the rash is generally accepted as the sign of postherpetic neuralgia. Sometimes serious effects including partial facial paralysis (usually temporary), ear damage, or encephalitis may occur. Shingles on the upper half of the face (the first branch of the trigeminal nerve) may result in eye damage and require urgent ophthalmological assessment. Ocular complications occur in approximately one half of patients with involvement of the ophthalmic division of the trigeminal nerve. These complications include mucopurulent conjunctivitis, episcleritis, keratitis and anterior uveitis. Cranial nerve palsies of the third, fourth and sixth cranial nerves may occur, affecting extraocular motility.
Since shingles is a reactivation of a virus contracted previously—often decades earlier—it cannot be induced by exposure to another person with shingles or chickenpox. Those with active blisters, however, can spread chickenpox to others who have never had that condition and who have not been vaccinated against it.
|1.||Back or underarm pain and small rash spots appear|
|2.||Rash (itchy for some) spreads around the body|
|3.||More pain develops|
|4.||Bubbles filled with fluid pop up|
|5.||After 4-5 weeks pain is gone and bubbles turn dark purple and peel off|
Acrochordons (Skin Tags)
Acrochordons, or skin tags, are small benign tumors that form primarily in areas where the skin forms creases, such as the neck, armpits, and groin. They also occur on the face, usually on the eyelids. They range in size from two to five millimeters, although larger ones have been seen. The surface of acrochordons may be smooth or irregular in appearance. Often, they are raised from the surface of the skin on a fleshy stalk called a “peduncle.” Microscopically, an acrochordon consists of a fibrovascular core, sometimes also with fat cells, covered by an unremarkable epidermis.
Skin tags are harmless, although they are sometimes irritated by clothing or jewelry. Why and how skin tags form is not entirely known, but there are correlations with age and obesity. They are more common in people with diabetes mellitus and in pregnant women. It is estimated that by age 70, up to 59 percent of people have them. A genetic component (causation) is thought to exist. Prior to the age of modern medicine, acrochordons were believed to be one sign of a witches’ mark.
There are several methods of removing acrochordons:
|tying off the stem to cut off the blood supply|
|excision with scissors or a scalpel|
|burning with an electric needle|
All of these methods of treatment are considered minor surgery, typically done in a doctor’s office. Since removal of skin tags is considered to be cosmetic, most health care systems and medical insurance plans will not cover it.
Skin Cancer (Carcinoma)
Skin cancer is a malignant growth on the skin, which can have many causes, including repeated severe sunburn or long-term exposure to the sun. Skin cancer generally develops in the epidermis, the outermost layer of skin, so a tumor is usually clearly visible. This makes most skin cancers detectable in the early stages. There are three common types of skin cancer each of which are named after the type of skin cell. In the case of UV damage, sun screen is one of the better forms of prevention.
The most common types are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) which may be locally disfiguring but unlikely to spread to other parts of the body. The most dangerous type is malignant melanoma, which can be fatal if not treated early, but forms only a small proportion of all skin cancers.
Other types of skin cancer are:
|Merkel cell carcinoma|
Skin cancer is an increasingly common condition, in part attributed to increased exposure to ultraviolet radiation. The increased exposure is mainly due to the recent popularity of sun tanning (sun bathing). Lighter-skinned individuals are more vulnerable. In the United States, about one out of every three new cancers arises from skin. Skin cancers are often curable. Barriers which reduce UV exposure are effective in preventing skin cancers (clothes, hats, creams, lotions).
Minor surface skin cancers are readily treatable by simple surgery, but if the cancer is allowed to grow then it will penetrate through the layers of skin and affect the lymphatic system. It may also metastasize and spread to other parts of the body.
Skin cancers which are aggressive, recurrent, or located upon ‘high risk sites’ of the body (central face, scalp, ears, genitalia) may require more advanced surgical approaches such as Mohs’ micrographic surgery to achieve high cure rates.
Signs and symptoms
There are a variety of different skin cancer symptoms. These include sores or changes in the skin that do not heal, ulcers in the skin, discoloring in parts of the skin, and changes in existing moles.
|Basal cell carcinoma usually looks like a raised, smooth, pearly bump on the sun-exposed skin of the head, neck or shoulders. Sometimes small blood vessels can be seen within the tumor. Crusting and bleeding in the center of the tumour frequently develops. It is often mistaken for a sore that does not heal.|
|Squamous cell carcinoma is commonly a red, scaling, thickened patch on sun-exposed skin. Ulceration and bleeding may occur. When SCC is not treated, it may develop into a large mass.|
|Most melanomas are brown to black looking lesions. Signs that might indicate a malignant melanoma include change in size, shape, color or elevation of a mole. The appearance of a new mole during adulthood, or new pain, itching, ulceration or bleeding of an existing mole should be checked.|
Non-melanoma skin cancer
(Non-melanoma skin cancers include basal cell carcinoma and squamous cell carcinoma.)
|reducing exposure to ultraviolet (UV) radiation|
|changing patterns of outdoor activities, sun exposure avoidance 11 am – 3 pm|
|wearing protective clothing (long sleeves and hats) when outdoors|
|using efficient sunscreens is recommended. It is a simple step to reduce your chance of cancer. You should wear some type of sunscreen everyday.|
|avoiding sunburns, especially in childhood and adolescence|
|reducing exposure to ultraviolet (UV) radiation|
|changing patterns of outdoor activities, sun exposure avoidance 10 am – 4 pm|
|wearing protective clothing (long sleeves and hats) when outdoors|
It is generally accepted that UV exposure is the greatest risk factor in melanoma development but skeptics have noted that there is absolutely no proven data that links moderate sun exposure with the appearance of melanoma.
There is a lot of controversy in the medical community regarding the role of sunlight to skin cancer. Michael F. Holick, MD, PhD, a professor at Boston University, based on research, advocates moderate sun light exposure, which would facilitate vitamin D production in human body, as a mean to prevent skin cancer, as well as other forms of cancer. However, he was asked to resign his post in 2004 by Department chair Barbara Gilchrest, MD, for presenting a view that conflicts with that from American Academy of Dermatology that any sunlight exposure would increase the risk of skin cancer.
Squamous cell carcinoma is a malignant epithelial tumor which originates in epidermis, squamous mucosa or areas of squamous metaplasia.
Macroscopically, the tumor is often elevated, fungating, or may be ulcerated with irregular borders. Microscopically, tumor cells destroy the basement membrane and form sheets or compact masses which invade the subjacent connective tissue (dermis). In well differentiated carcinomas, tumor cells are pleomorphic/atypical, but resembling normal keratinocytes from prickle layer (large, polygonal, with abundant eosinophilic (pink) cytoplasm and central nucleus). Their disposal tends to be similar to that of normal epidermis: immature/basal cells at the periphery, becoming more mature to the center of the tumor masses. Tumor cells transform into keratinized squamous cells and form round nodules with concentric, laminated layers, called “cell nests” or “epithelial/keratinous pearls”. The surrounding stroma is reduced and contains inflammatory infiltrate (lymphocytes). Poorly differentiated squamous carcinomas contain more pleomorphic cells and no keratinization.
Psoriasis is an immune-mediated disease which affects the skin and joints. It commonly causes red scaly patches to appear on the skin. The scaly patches caused by psoriasis, called psoriatic plaques or lesions, are areas of excessive skin production and inflammation. Skin rapidly accumulates at these sites and takes a silvery-white appearance. Plaques frequently occur on the skin of the elbows and knees, but can affect any area including the scalp and genitals. Psoriasis is not contagious.
The disorder is a chronic recurring condition which varies in severity from minor localized patches to complete body coverage. Fingernails and toenails are frequently affected (psoriatic nail dystrophy). Psoriasis can also cause inflammation of the joints, which is known as psoriatic arthritis. Ten to fifteen percent of people with psoriasis have psoriatic arthritis.
Several factors are thought to aggravate psoriasis. These include stress and excessive alcohol consumption. Individuals with psoriasis may suffer from depression and loss of self-esteem. As such, quality of life is an important factor in evaluating the severity of the disease. There are many treatments available but because of its chronic recurrent nature psoriasis is a challenge to treat.
Psoriasis is probably one of the longest known illnesses of humans and simultaneously one of the most misjudged and misunderstood. Some scholars believe psoriasis to have been included among the skin conditions called tzaraat in the Bible. In more recent times psoriasis was frequently described as a variety of leprosy. It became known as Willan’s lepra in the late 18th century when English dermatologists Robert Willan and Thomas Bateman differentiated it from other skin diseases and provided the first rational nomenclature based on the appearance of lesions. Willan identified two categories: leprosa graecorum and psora leprosa.
While it may have been visually, and later semantically, confused with leprosy it was not until 1841 that the condition was finally given the name psoriasis by the Viennese dermatologist Ferdinand von Hebra. The name is derived from the Greek word psora which means to itch.
It was during the 20th century that psoriasis was further differentiated into specific types.
Types of psoriasis
The symptoms of psoriasis can manifest in a variety of forms. Variants include plaque, pustular, guttate and flexural psoriasis. This section describes each type (with ICD-10 code).
Photograph of an arm covered
with plaque psoriasis.
|Plaque psoriasis (psoriasis vulgaris) (L40.0) is the most common form of psoriasis. It affects 80 to 90% of people with psoriasis. Plaque psoriasis typically appears as raised areas of inflamed skin covered with silvery white scaly skin. These areas are called plaques.Flexural psoriasis (inverse psoriasis) (L40.83-4) appears as smooth inflamed patches of skin. It occurs in skin folds, particularly around the genitals, the armpits, and under the breasts. It is aggravated by friction and sweat, and is vulnerable to fungal infections.
Guttate psoriasis (L40.4) is characterized by numerous small oval (teardrop-shaped) spots. These numerous spots of psoriasis appear over large areas of the body, such as the trunk, limbs, and scalp. Guttate psoriasis is associated with streptococcal throat infection.
Pustular psoriasis (L40.1-3, L40.82) appears as raised bumps that are filled with non-infectious pus (pustules). The skin under and surrounding pustules is red and tender. Pustular psoriasis can be localized, commonly to the hands and feet (palmoplantar pustulosis), or generalized with widespread patches occurring randomly on any part of the body.
Nail psoriasis (L40.86) produces a variety of changes in the appearance of finger and toe nails. These changes include discoloring under the nail plate, pitting of the nails, lines going across the nails, thickening of the skin under the nail, and the loosening (onycholysis) and crumbling of the nail.
Psoriatic arthritis (L40.5) involves joint and connective tissue inflammation. Psoriatic arthritis can affect any joint but is most common in the joints of the fingers and toes. This can result in a sausage-shaped swelling of the fingers and toes known as dactylitis. Psoriatic arthritis can also affect the hips, knees and spine (spondylitis). About 10-15% of people who have psoriasis also have psoriatic arthritis.
Erythrodermic psoriasis (L40.85) involves the widespread inflammation and exfoliation of the skin over most of the body surface. It may be accompanied by severe itching, swelling and pain. It is often the result of an exacerbation of unstable plaque psoriasis, particularly following the abrupt withdrawal of systemic treatment. This form of psoriasis can be fatal, as the extreme inflammation and exfoliation disrupt the body’s ability to regulate temperature and for the skin to perform barrier functions.
A diagnosis of psoriasis is usually based on the appearance of the skin. There are no special blood tests or diagnostic procedures for psoriasis. Sometimes a skin biopsy, or scraping, may be needed to rule out other disorders and to confirm the diagnosis. Histologically, skin from a biopsy will show clubbed Rete ridges if positive for psoriasis.
Psoriasis is usually graded as mild (affecting less than 3% of the body), moderate (affecting 3-10% of the body) or severe. Several other scales exist for measuring the severity of psoriasis. These scales are generally based on the following factors: the proportion of body surface area affected; disease activity (degree of plaque redness, thickness and scaling); response to previous therapies; and the impact of the disease on the person.
The Psoriasis Area Severity Index (PASI) is the most widely used measurement tool for psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease).
Effect on the quality of life
Psoriasis has been shown to affect health-related quality of life to an extent similar to the effects of other chronic diseases such as depression, myocardial infarction, hypertension, congestive heart failure or type 2 diabetes. Depending on the severity and location of outbreaks, individuals may experience significant physical discomfort and some disability. Itching and pain can interfere with basic functions, such as self-care, walking, and sleep. Plaques on hands and feet can prevent individuals from working at certain occupations, playing some sports, and caring for family members or a home. The frequency of medical care is costly and can interfere with an employment or school schedule.
Individuals with psoriasis may also feel self-conscious about their appearance and have a poor self-image that stems from fear of public rejection and psychosexual concerns. Psychological distress can lead to significant depression and social isolation.
Over time, psoriasis can become resistant to a specific therapy. Treatments may be periodically changed to prevent resistance developing (tachyphylaxis) and to reduce the chance of adverse reactions occurring. This is called treatment rotation.
Bath solutions and moisturizers help sooth affected skin and reduce the dryness which accompanies the build-up of skin on psoriatic plaques. Medicated creams and ointments applied directly to psoriatic plaques can help reduce inflammation, remove built-up scale, reduce skin turn over, and clear affected skin of plaques. Ointment and creams containing coal tar, dithranol (anthralin), corticosteroids, vitamin D3 analogues (for example, calcipotriol), and retinoids are routinely used. The mechanism of action of each is probably different but they all help to normalize skin cell production and reduce inflammation.
The disadvantages of topical agents are variabily that they can often irritate normal skin, can be time consuming and awkward to apply, cannot be used for long periods, can stain clothing or have a strong odor. As a result, it is sometimes difficult for people to maintain the regular application of these medications. Abrupt withdrawal of some topical agents, particularly corticosteroids, can cause an aggressive recurrence of the condition. This is known as a rebound of the condition.
Some topical treatments with innovative concepts and cosmetic feel are coming into the market (for example Dermist cream in India). Though these claimed to be side-effects free, cosmetically adjusted for day time use and safe for long term use; these are non-conventional medicines, comes under traditional system of ayurveda hence not very popular in the western world. Some topical agents are used in conjunction with other therapies, especially phototherapy.
It has long been recognized that daily, short, non-burning exposure to sunlight helped to clear or improve psoriasis. Niels Finsen was the first physician to investigate the therapeutic effects of sunlight scientifically and to use sunlight in clinical practice. This became known as phototherapy.
Sunlight contains many different wavelengths of light. It was during the early part of the 20th century that it was recognized that for psoriasis the therapeutic property of sunlight was due to the wavelengths classified as ultraviolet (UV) light.
Ultraviolet wavelengths are subdivided into UVA (380–315 nm), UVB (315–280 nm), and UVC (< 280 nm). Ultraviolet B (UVB) (315–280 nm) is absorbed by the epidermis and has a beneficial effect on psoriasis. Narrowband UVB (311 to 312 nm), is that part of the UVB spectrum that is most helpful for psoriasis. Exposure to UVB several times per week, over several weeks can help people attain a remission from psoriasis.
Ultraviolet light treatment is frequently combined with topical (coal tar, calcipotriol) or systemic treatment (retinoids) as there is a synergy in their combination. The Ingram regime, involves UVB and the application of anthralin paste. The Goeckerman regime combines coal tar ointment with UVB.
Psoralen and ultraviolet A phototherapy (PUVA) combines the oral or topical administration of psoralen with exposure to ultraviolet A (UVA) light. Precisely how PUVA works is not known. The mechanism of action probably involves activation of psoralen by UVA light which inhibits the abnormally rapid production of the cells in psoriatic skin. There are multiple mechanisms of action associated with PUVA, including effects on the skin immune system.
Dark glasses must be worn during PUVA treatment because there is a risk of cataracts developing from exposure to sunlight. PUVA is associated with nausea, headache, fatigue, burning, and itching. Long-term treatment is associated with squamous-cell and melanoma skin cancers.
Psoriasis which is resistant to topical treatment and phototherapy is treated by medications that are taken internally by pill or injection. This is called systemic treatment. Patients undergoing systemic treatment are required to have regular blood and liver function tests because of the toxicity of the medication. Pregnancy must be avoided for the majority of these treatments. Most people experience a recurrence of psoriasis after systemic treatment is discontinued.
The three main traditional systemic treatments are the immunosupressant drugs methotrexate and ciclosporin, and retinoids, which are synthetic forms of vitamin A. Other additional drugs, not specifically licensed for psoriasis, have been found to be effective. These include the antimetabolite tioguanine, the cytotoxic agent hydroxyurea, sulfasalazine, the immunosupressants mycophenolate mofetil, azathioprine and oral tacrolimus. These have all been used effectively to treat psoriasis when other treatments have failed. Although not licensed in many other countries fumaric acid esters have also been used to treat severe psoriasis in Germany for over 20 years.
Biologics are manufactured proteins that interrupt the immune process involved in psoriasis. Unlike generalised immunosuppressant therapies such as methotrexate, biologics focus on specific aspects of the immune function leading to psoriasis. These drugs are relatively new, and their long-term impact on immune function is unknown. They are very expensive and only suitable for very few patients with psoriasis.
|Antibiotics are not indicated in routine treatment of psoriasis. However, antibiotics may be employed when an infection, such as that caused by the bacteria Streptococcus, triggers an outbreak of psoriasis, as in certain cases of guttate psoriasis.|
|Climatotherapy involves the notion that some diseases can be successfully treated by living in particular climate. Several psoriasis clinics are located throughout the world based on this idea. The Dead Sea is one of the most popular locations for this type of treatment.|
|In Turkey, doctor fish which live in the outdoor pools of spas, are encouraged to feed on the psoriatic skin of people with psoriasis. The fish only consume the affected areas of the skin. The outdoor location of the spa may also have a beneficial effect. This treatment can provide temporary relief of symptoms. A revisit to the spas every few months is often required.|
|Some people subscribe to the view that psoriasis can be effectively managed through a healthy lifestyle. This view is based on anecdote, and has not been subjected to formal scientific evaluation. Nevertheless, some people report that minimizing stress and consuming a healthy diet, combined with rest, sunshine and swimming in saltwater keep lesions to a minimum. This type of “lifestyle” treatment is suggested as a long-term management strategy, rather than an initial treatment of severe psoriasis.|
|A number of patients have reported significant improvements from sun and sea water: unfortunately, salt alone does not have any effect. Sea water contains so many minerals and different life forms (thousands of species of bacteria alone that it will be hard to determine which of these is causing the observed effects.|
|Some psoriasis patients use herbology as a holistic approach that aims to treat the underlying causes of psoriasis.|
|A psychological symptom management program has been reported as being a helpful adjunct to traditional therapies in the management of psoriasis.|
|It is claimed that Epsom salt may have a positive effect in reducing the effects of psoriasis.|
|The use of Neem oil in India has been in documented for 6000 years.|
|It is claimed that yoga and meditative practices help psoriasis patients by ‘detoxifying’ the body any by the reduction of stress.|
The history of psoriasis is littered with treatments of dubious effectiveness and high toxicity. These treatments received brief popularity at particular time periods or within certain geographical regions. The application of cat feces to red lesions on the skin, for example, was one of the earliest topical treatments employed in ancient Egypt. Onions, sea salt and urine, goose oil and semen, wasp droppings in sycamore milk, and soup made from vipers have all been reported as being ancient treatments.
In the more recent past Fowler’s solution, which contains a poisonous and carcinogenic arsenic compound, was used by dermatologists as a treatment for psoriasis during the 18th and 19th centuries. Grenz Rays (also called ultrasoft X-rays or Bucky rays) was a popular treatment of psoriasis during the middle of the 20th century. This type of therapy was superseded by ultraviolet therapy. Undecylenic acid was investigated and used for psoriasis some 40 years ago. All these treatments have fallen out of favor.
Future drug development
Historically, agents used to treat psoriasis were discovered by experimentation or by accident. In contrast, current novel therapeutic agents are designed from a better understanding of the immune processes involved in psoriasis and by the specific targeting of molecular mediators. Examples can be seen in the use of biologics which target T cells and TNF inhibitors.
Psoriasis is a chronic lifelong condition. There is currently no cure but various treatments can help to control the symptoms. Many of the most effective agents used to treat severe psoriasis carry an increased risk of significant morbidity including skin cancers, lymphoma and liver disease. However, the majority of people’s experience of psoriasis is that of minor localized patches, particularly on the elbows and knees, which can be treated with topical medication. Psoriasis does get worse over time but it is not possible to predict who will go on to develop extensive psoriasis or those in whom the disease may appear to vanish. Individuals will often experience flares and remissions throughout their life. Controlling the signs and symptoms typically requires lifelong therapy.
“The heartbreak of psoriasis”
The phrase “the heartbreak of psoriasis” is often used both seriously and ironically to describe the emotional impact of the disease. It can be found in various advertisements for topical and other treatments; conversely, it has been used to mock the tendency of advertisers to exaggerate (or even fabricate) aspects of a malady for financial gain. (In Bloom County, the character of Opus once considered the possibility of his suffering from “the heartbreak of nose hemorrhoids.”) While many products today use the phrase in their advertising, it originated in a 1960s advertising campaign for Tegrin®, a coal tar-based medicated soap.
Eczema is a form of dermatitis, or inflammation of the upper layers of the skin. The term eczema is broadly applied to a range of persistent or recurring skin rashes characterized by redness, skin edema, itching and dryness, with possible crusting, flaking, blistering, cracking, oozing or bleeding. Areas of temporary skin discoloration sometimes characterize healed lesions, though scarring is rare.
ICD-10 codes are provided where available.
The term eczema refers to a set of clinical characteristics. Classification of the underlying diseases has been haphazard and unsystematic, with many synonyms used to describe the same condition. A type of eczema may be described by location (e.g. hand eczema), by specific appearance (eczema craquele or discoid), or by possible cause (varicose eczema). Further adding to the confusion, many sources use the term eczema and the term for the most common type of eczema (atopic eczema) interchangeably.
More severe eczema
The European Academy of Allergology and Clinical Immunology (EAACI) has published a position paper which simplifies the nomenclature of allergy-related diseases including atopic and allergic contact eczemas (Johansson et al., 2001, Allergy 56:813). Non-allergic eczemas are not affected by this proposal. The classification below is clustered by incidence frequency.
More common eczemas
|Atopic eczema (aka infantile e., flexural e., atopic dermatitis) is believed to have a hereditary component, and often runs in families whose members also have hay fever and asthma. Itchy rash is particularly noticeable on face and scalp, neck, inside of elbows, behind knees, and buttocks. Experts are urging doctors to be more vigilant in weeding out cases that are in actuality irritant contact dermatitis. It is very common in developed countries, and rising.|
|Contact dermatitis is of two types: allergic (resulting from a delayed reaction to some allergen, such as poison ivy or nickel), and irritant (resulting from direct reaction to, say, a solvent). Some substances act both as allergen and irritant (e.g. wet cement). Other substances cause a problem after sunlight exposure, bringing on phototoxic dermatitis. About three quarters of cases of contact eczema are of the irritant type, which is the most common occupational skin disease. Contact eczema is curable provided the offending substance can be avoided, and its traces removed from one’s environment.|
|Xerotic eczema (aka asteatotic e., e. craquele or craquelatum, winter itch, pruritus hiemalis) is dry skin that becomes so serious it turns into eczema. It worsens in dry winter weather, and limbs and trunk are most often affected. The itchy, tender skin resembles a dry, cracked, river bed. This disorder is very common among the older population. Ichthyosis is a related disorder.|
|Seborrhoeic dermatitis (aka cradle cap in infants, dandruff) causes dry or greasy scaling of the scalp and eyebrows. Scaly pimples and red patches sometimes appear in various adjacent places. In newborns it causes a thick, yellow crusty scalp rash called cradle cap which seems related to lack of biotin, and is often curable.|
Less common eczemas
|Dyshidrosis (aka dyshidrotic e., pompholyx, vesicular palmoplantar dermatitis, housewife’s eczema) only occurs on palms, soles, and sides of fingers and toes. Tiny opaque bumps called vesicles, thickening, and cracks are accompanied by itching which gets worse at night. A common type of hand eczema, it worsens in warm weather. (L30.1)|
|Discoid eczema (aka nummular e., exudative e., microbial e.) is characterized by round spots of oozing or dry rash, with clear boundaries, often on lower legs. It is usually worse in winter. Cause is unknown, and the condition tends to come and go. (L30.0)|
|Venous eczema (aka gravitational e., stasis dermatitis, varicose e.) occurs in people with impaired circulation, varicose veins and edema, and is particularly common in the ankle area of people over 50. There is redness, scaling, darkening of the skin and itching. The disorder predisposes to leg ulcers.|
|Dermatitis herpetiformis (aka Duhring’s Disease) causes intensely itchy and typically symmetrical rash on arms, thighs, knees, and back. It is directly related to celiac disease, and can often be put into remission with appropriate diet.|
|Neurodermatitis (aka lichen simplex chronicus, localized scratch dermatitis) is an itchy area of thickened, pigmented eczema patch that results from habitual rubbing and scratching. Usually there is only one spot. Often curable through behavior modification and anti-inflammatory medication. Prurigo nodularis is a related disorder showing multiple lumps.|
|Autoeczematization (aka id reaction, autosensitization) is an eczematous reaction to an infection with parasites, fungi, bacteria or viruses. It is completely curable with the clearance of the original infection that caused it. The appearance varies depending on the cause. It always occurs some distance away from the original infection.|
|There are also eczemas overlaid by viral infections (e. herpeticum, e. vaccinatum), and eczemas resulting from underlying disease (e.g. lymphoma). Eczemas originating from ingestion of medications, foods, and chemicals, have not yet been clearly systematized. Other rare eczematous disorders exist in addition to those listed here.|
Eczema diagnosis is generally based on the appearance of inflamed, itchy skin in eczema sensitive areas such as face, chest and other skin crease areas. For evaluation of the eczema, a scoring system can be used (for example, SCORAD, a scoring system for atopic dermatitis).
Given the many possible reasons for eczema flare ups, a doctor is likely to ascertain a number of other things before making a judgment:
|An insight to family history|
|Any prescribed drug intake|
|Any chemical or material exposure at home or workplace|
To determine whether an eczema flare is the result of an allergen, a doctor may test the blood for the levels of antibodies and the numbers of certain types of cells. In eczema, the blood may show a raised IgE or an eosinophilia.
The blood can also be sent for a specific test called Radioallergosorbent Test (RAST) or a Paper Radioimmunosorbent Test (PRIST). In the test, blood is mixed separately with many different allergens and the antibody levels measured. High levels of antibodies in the blood signify an allergy to that substance.
Another test for eczema is skin patch testing. The suspected irritant is applied to the skin and held in place with an adhesive patch. Another patch with nothing is also applied as a control. After 24 to 48 hours, the patch is removed. If the skin under the suspect patch is red and swollen, the result is positive and the person is probably allergic to that substance.
Occasionally, the diagnosis may also involve a skin biopsy: removal of a small piece of affected skin for microscopic examination in a pathology laboratory.
Blood tests and biopsies are not always necessary for eczema diagnosis. However, doctors will at times require them if the symptoms are unusual, severe or in order to identify particular triggers.
Dermatitis severely dries out the skin, and keeping the affected area moistened can promote healing and retain natural moisture. This is the most important self-care treatment that one can use in atopic eczema.
The use of anything that may dry out the skin should be discontinued and this includes both normal soaps and bubble baths that remove the natural oils from the skin.
The moistening agents are called ’emollients’. The rule to use is: match the thicker ointments to the driest, flakiest skin. Light emollients like Aqueous Cream may dry the skin if it is very flaky.
Emollient bath oils should be added to bath water and then suitable agents applied after patting the skin dry. Generally twice daily applications of emollients work best and while creams are easy to apply, they are quickly absorbed into the skin, therefore needing frequent re-application. Ointments, with less water content, stay on the skin for longer and need fewer applications.
Typical emollients are: Oilatum or Balneum bath oils, Medi Oil, Aqueous cream for washing with, Diprobase or Doublebase pump-action creams also used for washing and may be later applied directly to the skin.Sebexol, Epaderm ointment and Eucerin lotion or cream may be helpful with itching. Moisturizing gloves can be worn while sleeping.
Eczema and detergents
The first and primary recommendation is that people suffering from eczema shouldn’t use detergents of any kind unless absolutely necessary. Current medical thought is that people wash too much and that eczema sufferers should use cleansers only when water is not sufficient to remove dirt from skin.
Another point of view is that detergents are so ubiquitous in modern environments and so persistent in tissues and surfaces, safe soaps are necessary to remove them in order to eliminate the eczema in a percentage of cases. Although most recommendations use the terms “detergents” and “soaps” interchangeably, and tell eczema sufferers to avoid both, detergents and soaps are not the same and are not equally problematic to eczema sufferers. Detergents increase the permeability of skin membranes in a way that soaps and water alone do not. Sodium lauryl sulfate, the most common household detergent, has been shown to amplify the allergenicity of other substances (“increase antigen penetration”)
The use of detergents in recent decades has increased dramatically, while the use of soaps began to decline when detergents were invented, and leveled off to a constant around the ’60s. Complicating this picture is the recent development of mild plant-based detergents for the natural products sector.
Unfortunately there is no one agreed upon best kind of cleanser for eczema sufferers. Different clinical tests, sponsored by different personal product companies, unsurprisingly tout various brands as the most skin friendly based on specific properties of various products and different underlying assumptions as to what really determines skin friendliness. The terms “hypoallergenic” and “doctor tested” are not regulated (according to Consumer Reports®), and no research has been done showing that products labeled “hypoallergenic” are in fact less problematic than any others.
Dermatological recommendations in choosing a soap generally include:
|Avoid harsh detergents or drying soaps.|
|Choose a soap that has an oil or fat base; a “superfatted” soap is best.|
|Use an unscented soap.|
|Patch test your soap choice, by using it only on a chosen area until you are sure of its results.|
|Use a non-soap based cleanser.|
How to use soap when one must
|Use soap sparingly|
|Avoid using washcloths, sponges, or loofahs|
|Use soap only on areas where it is necessary|
|Soap up only at the very end of your bath|
|Use a fragrance free barrier type moisturizer such as vaseline® or aquaphor® before drying off|
|Use care when selecting lotion, soap, or fragrance, avoiding suspected allergens. Ask your doctor for recommendations.|
Never rub your skin dry, or else your skin’s oil/moisture will be on the towel and not your body
Antihistamine medication may reduce the itch during a flare up of eczema, and the reduced scratching in turn reduces damage & irritation to the skin (the Itch cycle).
Capsaicin applied to the skin acts as a counter irritant (see Gate control theory of nerve signal transmission). Other agents that act on nerve transmissions, like menthol, also have been found to mitigate the body’s itch signals, providing some relief. Recent research suggests Naloxone hydrochloride and dibucaine suppress the itch cycle in atopic-dermatitis model mice as well.
Dermatitis is often treated by doctors with prescribed Glucocorticoid (a corticosteroid steroid) ointments, creams or lotions. For mild-moderate eczema a weak steroid may be used (e.g. Hydrocortisone or Desonide), whilst more severe cases require a higher-potency steroid (e.g. Clobetasol propionate). They cannot cure eczema, but are highly effective in controlling, or suppressing, symptoms in most cases. It is believed by alternative health practitioners that the suppression of eczema can often cause more serious health complaints, such as asthma.
Corticosteroids must be used sparingly to avoid possible side effects, the most significant of which is that their prolonged use can cause the skin to thin and become fragile (atrophy). High strength steroids used over large areas may be significantly absorbed into the body causing bone demineralisation (osteoporosis). Finally by their immunosuppression action they can, if used alone, exacerbate some skin infections (fungal or viral). If using on the face, only a low strength steroid should be used and care must be taken to avoid the eyes.
Hence, a steroid of an appropriate strength to promptly settle an episode of eczema should be sparingly applied. Once the desired response has been achieved it should be discontinued and replaced with emollients as maintenance therapy.
Topical immunomodulators like pimecrolimus (Elidel® and Douglan®) and tacrolimus (Protopic®) were developed after corticosteroid treatments, effectively suppressing the immune system in the affected area, and appear to yield better results in some populations. However, such suppression is believed by alternative health practitioners to have possible adverse health effects. The US Food and Drug Administration has issued a public health advisory about the possible risk of lymph node or skin cancer from use of these products, but many professional medical organizations disagree with the FDA’s findings:
|The postulation is that the immune system may help remove some pre-cancerous abnormal cells which is prevented by these drugs. However, any chronic inflammatory condition such as eczema, by the very nature of increased metabolism and cell replication, has a tiny associated risk of cancer (see Bowen’s disease).|
|Current practice by UK dermatologists is not to consider this a significant real concern and they are increasingly recommending the use of these new drugs. The dramatic improvement on the condition can significantly improve the quality of life of sufferers (and families kept awake by the distress of affected children). The major debate, in the UK, has been about the cost of such newer treatments and, given only finite NHS resources, when they are most appropriate to use.|
|In addition to cancer risk, there are other potential side effects with this class of drugs. Adverse reactions including severe flushing, photosensitive reactivity and possible drug interaction in patients who consume even small amounts of alcohol.|
The disruption to the skin’s normal barrier protection through dry and cracked skin allows easy entry for bacteria. Scratching by the patient both introduces infection and spreads it from one area to another. Any skin infection further irritates the skin and a rapid deterioration in the condition may ensue; the appropriate antibiotic should be given.
Eczema often comes and goes in cycles, meaning that at some times of the year sufferers are able to feel normal, while at other times they will distance themselves from social contact. Sufferers with visible marks generally feel fine (physically) and can act normal, but when it is mentioned they may become withdrawn and self-conscious. Since it is a condition made worse by scratching, a sufferer with highly visible sores aggravated by scratching often feel as if everyone is looking at the marks and that it is self induced. Although scratching does give a sense of release, it is usually a temporary solution and can lead to problems with constant scratching. Sufferers often shy away from scratching in public, but the solution is to scratch in privacy. In cases of children with eczema, visible scars or scratch marks can lead to suspicion of home abuse or self-mutilation, which causes possible peer rejection and may add to a general level of stress.
Light therapy using ultraviolet light can help. UVA is mostly used but UVB and Narrow Band UVB are also used. Ultraviolet light exposure carries its own risks, particularly later skin cancers. When light therapy alone is found to be ineffective, it is combined with a substance called psoralen. This PUVA (Psoralen + UVA) combination therapy is termed photo-chemotherapy. Psoralens make the skin more sensitive to UV light, allowing lower doses of UVA to be used.
Diet and Nutrition
Recent studies provide hints that food allergy may trigger atopic dermatitis. For these people, identifying the allergens could allow an avoidance diet, although this approach is still in an experimental stage.
Dietary elements reported to trigger Eczema by sufferers include dairy products and coffee (both caffeinated and decaffeinated), soya, eggs, nuts and wheat.
Non-conventional medical approaches include traditional herbal medicine and homeopathy. Patients should inform their doctor/allergist/dermatologist if they are pursuing one of these treatment routes.
Historical sources – notably traditional Chinese medicine and Western herbalism – suggest a wide variety of treatments, each of which may vary from individual to individual as to efficacy or harm. Toxicity may be present in some. Some of these remedies are for topical use, some are to be ingested.
|Ledeboureilla seseloides||Azadirachta indica|
|Potentilla chinensis||evening primrose oil|
|Aebia clematidis||Tea Tree Oil (Melaleuca Oil)|
|Paeonia lactiflora (Chinese Peony)||calamine|
|Dictamnus dasycarpus||crocodile oil|
|Tribulus terrestris||cod liver oil|
|Glycyrrhiza uralensis||neem oil|
|Glycyrrhiza glabra (Licorice)||Aloe Propolis cream|
|Schizonepeta tenuifolia (Neem)||Raw Goat’s Milk|
|Schizonepeta tennuifolia||Hemp Cream|
|Oatmeal in solution applied topically is also an alternative therapy.|
Homeopathic treatment aims to remove the underlying cause of the eczema by strengthening the immune system and improving general health. It is important that a remedy is tailored to the needs of the individual by a skilled, qualified practitioner, who takes a detailed history, because homeopathic medicines taken improperly can cause suppression, just as conventional medicines do. Treatment can take anywhere between a couple of months and 2 years, depending on the severity & duration of the eczema, the general level of health of the patient, and the degree of suppression (usually by corticosteroids).
A study carried out over a 6 year period at the Bristol Homeopathic Hospital, UK, looked at the clinical outcomes of homeopathic treatment of 448 eczema patients, aged 16 and under, many of whom had tried, but not been helped by, conventional medicine. The study found that 82% showed improvement following homeopathic treatment.
Other than direct treatments of the symptoms, no cure is presently known for most types of dermatitis; even cortisone treatments and immunomodulation may often have only minor effects on what may be a complex problem. As the condition is often related to family history of allergies (and thus heredity), it is probable that gene therapy or genetic engineering might help.
Damage from the enzymatic activity of allergens is usually prevented by the body’s own protease inhibitors, such as, LEKTI, produced from the gene SPINK5. Mutations in this gene are known to cause Netherton’s syndrome, which is a congenital erythroderma. These patients nearly always develop atopic disease, including hay fever, food allergy, urticaria and asthma. Such evidence supports the hypothesis that skin damage from allergens may be the cause of eczema, and may provide a venue for further treatment.
Another study identified a gene that the researchers believe to be the cause of inherited eczema and some related disorders. The gene produces the protein filaggrin, the lack of which causes dry skin.
Telangiectasia (Spider Veins)
Telangiectasias, or spider veins, are small enlarged blood vessels near the surface of the skin; usually they measure only a few millimeters. They can develop anywhere on the body but commonly on the face around the nose, cheeks, and chin. They can also develop on the legs, specifically on the upper thigh, below the knee joint, and around the ankles.
These are actually developmental abnormalities but can closely mimic the behavior of benign vascular neoplasms. They may be composed of abnormal aggregations of arterioles, capillaries, or venules.
Telangiectasias can result in naevus flammeus (port-wine stain), which is a flat birthmark on the head or neck that spontaneously regresses. A port-wine stain, if present, will grow proportionately with the child. There is a high association with Sturge-Weber syndrome, a nevus formation in the skin supplied by the trigeminal nerve and associated with glaucoma, meningeal angiomas, and mental retardation. Finally, spider telangiectasias are a radial array of tiny arterioles that commonly occur in pregnant women and in patients with hepatic cirrhosis. In men, they are related to high estrogen levels secondary to liver disease.
Telangiectasias are often treated with laser or IPL therapy. There have been medication based treatments available for over 50 years. A Sclerosant medication is injected into the diseased vein so it hardens and eventually shrinks away.
A wart is generally a small, rough tumour, typically on hands and feet, that resembles a cauliflower. Warts are common, and are caused by a viral infection, specifically by the human papillomavirus (HPV). They typically disappear after a few months but can last for years and can recur. A few papillomaviruses are known to cause cancer. Certain types of warts, depending on location and cause, can be contagious from region to region, but are not transferable between species.
Types of wart
A range of different types of wart have been identified, which differ in shape and site affected, as well as the type of human papillomavirus involved. These include:
|common wart (verruca vulgaris): a raised wart with roughened surface, most common on hands and knees|
|flat wart (verruca plana): a small, smooth flattened wart, tan or flesh coloured, which can occur in large numbers; most common on the face, neck, hands, wrists and knees|
|filiform or digitate wart: a thread- or finger-like wart, most common on the face, especially near the eyelids and lips|
|plantar wart (verruca, verruca pedis): a hard sometimes painful lump, often with multiple black specks in the center; usually only found on pressure points on the soles of the feet|
|mosaic wart: a group of tightly clustered plantar-type warts, commonly on the hands or soles of the feet|
|genital wart (venereal wart, condyloma acuminatum, verruca acuminata): wart affecting the genital areas|
|Treatments that may be prescribed by a medical professional include:
None of these treatments are very effective on single uses; the wart often returns after the skin has healed from the treatment, but repeated treatment should get rid of the wart permanently. As they disappear after a few months and maximally a few years, treatment is necessary only if the lesions are painful or are a cosmetic problem.
One review of 52 clinical trials of various cutaneous wart treatments concluded that topical treatments containing salicylic acid were the best supported, with an average cure rate of 75% observed with salicylic acid compared with 48% for placebo in six placebo-controlled trials including a total of 376 participants. The reviewers also concluded that there was little evidence of a significant benefit of cryotherapy over placebo or no treatment.
There are also several over-the-counter options. The most common ones involve salicylic acid. These products are readily available at most drugstores and supermarkets. There are typically two types of products: adhesive pads treated with salicylic acid, or a bottle of concentrated salicylic acid. Removing a wart with this method requires a strict regimen of cleaning the area, applying the salicylic acid, and removing the dead skin with a pumice stone or emery board. It may take up to 12 weeks to remove a stubborn wart.
Another over-the-counter product that can aid in wart removal is silver nitrate in the form of a caustic pencil, which is also available at drug stores. This method generally takes three to six daily treatments to be effective. The instructions must be followed to minimize staining of skin and clothing.
Over-the-counter cryosurgery kits are also available, however they can often cost 3 times as much as the previously named products.
Like prescription treatments, over-the-counter treatments usually require multiple applications, and are only necessary if the warts are problematic. Additionally, these treatments are capable of destroying healthy skin as well as warts, so caution must be exercised by those attempting them without medical supervision.
Duct tape occlusion therapy involves placing a piece of duct tape (or medical tape) over the affected area for a week at a time. The procedure is otherwise identical to that of using salicylic acid adhesive pads. One study found that the duct tape method was 85% effective, compared to a 60% success rate in the study’s cryotherapy group. Another study, however, found no statistically significant effect.
Other household remedies include the application of common household items, such as bruised garlic (held in place with a bandage or duct tape), banana skin, vinegar, hot water and washing liquid, aerosol sprays, tea tree oil and other natural oils, unskinned potatoes, potato or cauliflower juice, salt, or vegemite to the affected area. Milkweed or dandelion sap is also used. Anecdotal evidence suggests poison ivy can be effective (with extreme care). Accounts vary in regards to how long these remedies must be applied with each session and how long they take to work.
Without controlled studies for most household remedies, it is difficult to know whether the warts disappear because the remedies work, or if they disappear due to the individual’s own immune system response to the virus (possibly augmented by a placebo effect). The success of hypnosis in curing warts at least suggests that the condition may be cured by belief in a remedy, the placebo effect or other psychological means.
Some household remedies are potentially dangerous. These include attempts to cut or burn away the warts. Incense is sometimes used in Asian countries to burn warts. These methods are very painful, and can lead to infection and/or permanent scarring.
Botulinum Toxin (BOTOX)
Botulinum toxin is a neurotoxic protein produced by the bacterium Clostridium botulinum. It is one of the most poisonous naturally occurring substances in the world. Though it is highly toxic, it is used in minute doses both to treat painful muscle spasms, and as a cosmetic treatment in some parts of the world. It is sold commercially under the brand names Botox and Dysport for this purpose. The terms Botox and Dysport are trade names and are not used generically to describe the neurotoxins produced by Clostridia species.
The German physician and poet Justinus Kerner called botulinum toxin “sausage poison”, or “Canadian bacon pathogen” as this bacterium often causes poisoning by growing in badly handled or prepared meat products. He first conceived a possible therapeutic use of botulinum toxin. In 1870, Muller (another German physician) coined the name botulism, from Latin botulus = “sausage”. In 1895, Emile Van Ermengem first isolated the bacterium Clostridium botulinum. In 1944, Edward Schantz cultured Clostridium botulinum and isolated the toxin, and, in 1949, Burgen’s group discovered that botulinum toxin blocks neuromuscular transmission.
By 1973, Alan B Scott, MD, of Smith-Kettlewell Institute used botulinum toxin type A (BTX-A) in monkey experiments, and, in 1980, he officially used BTX-A for the first time in humans to treat strabismus. In December 1989, BTX-A (BOTOX) was approved by the US Food and Drug Administration (FDA) for the treatment of strabismus, blepharospasm, and hemifacial spasm in patients over 12 years old. The cosmetic effect of BTX-A was initially described by the Carruthers, a dermatologist/ophthalmologist husband and wife team working in Vancouver, Canada, although the effect had been observed by a number of independent groups. On April 15, 2002, the FDA announced the approval of botulinum toxin type A (BOTOX Cosmetic) to temporarily improve the appearance of moderate-to-severe frown lines between the eyebrows (glabellar lines). BTX-A has also been approved for the treatment of excessive underarm sweating. The acceptance of BTX-A use for the treatment of spasticity and muscle pain disorders is growing, with approvals pending in many European countries and studies on headaches (including migraine), prostatic symptoms, asthma, obesity and many other possible indications are ongoing.
Dysport is a therapeutic formulation of the type A toxin developed and manufactured in the UK and which is licenced for the treatment of focal dystonias and certain cosmetic uses in many territories world wide.
Botulinum Toxin Type B (BTX-B) received FDA approval for treatment of cervical dystonia on December 21, 2000. Trade names for BTX-B are Myobloc in the United States, and Neurobloc® in the European Union.
Researchers discovered in the 1950s that injecting overactive muscles with minute quantities of botulinum toxin type A decreased muscle activity by blocking the release of acetylcholine at the neuromuscular junction, thereby rendering the muscle unable to contract for a period of 4 to 6 months.
Alan Scott, a San Francisco ophthalmologist, first applied tiny doses of the toxin in a medicinal sense to treat crossed eyes and uncontrollable blinking, but needed a partner to gain regulatory approval to market his discovery as a drug. Allergan, Inc., a small pharmaceutical company that focused on prescription eye therapies and contact lens products, bought the rights to the drug in 1988 and received FDA approval in 1989. Allergan renamed the drug Botox.
Cosmetically desirable effects of Botox were quickly discovered thereafter when the frown lines between the eyebrows were observed to soften following treatment for eye muscle disorders, leading to clinical trials and subsequent FDA approval for cosmetic use in April 2002. As of 2006, Botox injection is the most common cosmetic operation in the United States.
Besides its cosmetic application, Botox is used in the treatment of:
|cervical dystonia (a neuromuscular disorder involving the head and neck)|
|blepharospasm (involuntary contraction of the eye muscles)|
|severe primary axillary hyperhidrosis (excessive sweating)|
Other uses of botulinum toxin type A that are widely known but not specifically approved by FDA include treatment of:
|overactive bladder syndrome with or without incontinence|
|spastic disorders associated with injury or disease of the central nervous system including trauma, stroke, multiple sclerosis, or cerebral palsy|
|focal dystonias affecting the limbs, face, jaw, or vocal cords|
|TMJ pain disorders|
In the Journal of Dermatologic Surgery, Eric Finzi claims to have treated clinically depressed patients with botox. On Good Morning America, he claimed that by taking away the ability to frown, he was somehow taking away the ability to feel depressed.
Treatment and prevention of chronic headache and chronic musculoskeletal pain are emerging uses for botulinum toxin type A. In addition, there is evidence that Botox may aid in weight loss by increasing the gastric emptying time.
Side effects can be predicted from the mode of action (muscle paralysis) and chemical structure (protein) of the molecule, resulting broadly speaking in two major areas of side effects: paralysis of the wrong muscle group and allergic reaction. Bruising at the site of injection is a side effect not of the toxin, but rather the mode of administration. In cosmetic use, this means that the client will complain of inappropriate facial expression such as drooping eyelid, uneven smile, loss of ability to close the eye. This will wear off in around 6 weeks. Bruising is prevented by the clinician applying pressure to the injection site, but may still occur, and will last around 7 – 10 days. When injecting the masseter muscle of the jaw, loss of muscle function will result in a loss or reduction of power to chew solid foods. All cosmetic treatments are of limited duration, and can be as short a period as six weeks, but usually one reckons with an effective period of between 3 and 6 months. At the extremely low doses used medicinally, botulinum toxin has a very low degree of toxicity.
There are seven serologically distinct toxin types, designated A through G; 3 subtypes of A have been described. The toxin is a two-chain polypeptide with a 100-kDa heavy chain joined by a disulphide bond to a 50-kDa light chain. This light chain is an enzyme (a protease) that attacks one of the fusion proteins at a neuromuscular junction, preventing vesicles from anchoring to the membrane to release acetylcholine. By inhibiting acetylcholine release, the toxin interferes with nerve impulses and causes paralysis of muscles in botulism.
It is possibly the most acutely toxic substance known, with a lethal dose of about 200-300 pg/kg, meaning that one hundred grams could kill every human on earth (for perspective, the rat poison strychnine, often described as highly toxic, has an LD50 of 1,000,000,000 pg/kg, and it would take forty million grams to kill every human).
It is also remarkably easy to come by: Clostridium spores are found in soil practically all over the earth.
Food-borne botulism usually results from ingestion of food that has become contaminated with spores (such as a perforated can) in an anaerobic environment, allowing the spores to germinate and grow. The growing (vegetative) bacteria produce toxin. It is the ingestion of preformed toxin that causes botulism, not ingestion of the spores or vegetative organism.
Infant (intestinal) and wound botulism both result from infection with spores which subsequently germinate, resulting in production of toxin and the symptoms of botulism.
The chemical is rapidly destroyed by heat, such as in thorough cooking.
Botulin toxin has always been considered an inferior agent for chemical warfare since it degrades rapidly on exposure to air, and therefore an area attacked with the toxic aerosol would be safe to enter within a day or so. In fact, the agent is so unstable that the medicinal form is generally shipped on dry ice. There are no documented cases of the toxin actually being used in warfare; however, it may have been used in the Operation Anthropoid to kill top Nazi Reinhard Heydrich and in “Operation Mongoose”, where in 1961, the CIA saturated some cigars, of Fidel Castro’s favorite brand, with botulinum toxin for a possible assassination attempt. The cigars were never used, but when tested years later were found still effective. The notorious Japanese biological warfare group Unit 731 fed botulinum to prisoners during Japan’s occupation of Manchuria in the 1930s.
There has been concern over the use of botulin toxin as a terrorist weapon, but it appears not to be ideal for this purpose. The vials used therapeutically are considered impractical as weapons because each vial contains only an extremely small fraction of the lethal dose. Nor is home-growing very viable; the bacterium in question is anaerobic and grows poorly in the presence of oxygen. This would make it difficult for terrorists to produce the toxin in bulk without specialized microbiological expertise.
The toxin’s properties did not escape the attention of the Aum Supreme Truth cult in Japan, who had set up a plant for bulk production of this agent, though their subway attacks used the nerve agent sarin instead, because of its easy dispersal and faster-acting properties.
Biochemical mechanism of toxicity
|The heavy chain of the toxin is particularly important for targeting the toxin to specific types of axon terminals. The toxin must get inside the axon terminals in order to cause paralysis. Following the attachment of the toxin heavy chain to proteins on the surface of axon terminals, the toxin can be taken into neurons by endocytosis. The light chain is able to leave endocytotic vesicles and reach the cytoplasm. The light chain of the toxin has protease activity. The type A toxin proteolytically degrades the SNAP-25 protein, a type of SNARE protein. The SNAP-25 protein is required for the release of neurotransmitters from the axon endings. Botulin toxin specifically cleaves these SNAREs, and so prevents neuro-secretory vesicles from docking/fusing with the nerve synapse plasma membrane and releasing their neurotransmitters.|
|Target molecules of botulinum (BoNT) and tetanus (TeNT) toxins inside
the axon terminal.
Though it affects the nervous system, common nerve agent treatments (namely the injection of atropine and 2-pam-chloride) will increase mortality by enhancing botulin toxin’s mechanism of toxicity. Attacks involving botulin toxin are distinguishable from those involving nerve agent in that NBC detection equipment (such as M-8 paper or the ICAM) will not indicate a “positive” when a sample of the agent is tested. Furthermore, botulism symptoms develop relatively slowly, over several days compared to nerve agent effects, which can be instantaneous.
Treatment of botulinum poisoning
The case fatality rate for botulinum poisoning from 1950-1996 was 15.5%, down from approximately 60% the 50-years prior. Death is generally secondary to respiratory failure due to paralysis of the respiratory muscles, so treatment consists of antitoxin administration and artificial ventilation. If initiated on time, these are quite effective. Occasionally, functional recovery may take several weeks to months.
There are two primary Botulinum Antitoxins available for treatment of botulism. Trivalent (A,B,E) Botulinum Antitoxin is derived from equine sources utilizing whole antibodies (Fab & Fc portions). This antitoxin is available from the local health department via the CDC. The second antitoxin is Heptavalent (A,B,C,D,E,F,G) Botulinum Antitoxin which is derived from “despeciated” equine IgG antibodies which have had the Fc portion cleaved off leaving the F(ab’)2 portions. This is a less immunogenic antitoxin that is effective against all known strains of botulism where not contraindicated. This is available from the US Army. On June 1, 2006 the US Department of Health and Human Services awarded a $363 million contract with Cangene Corporation for 200,000 doses of Heptavalent Botulinum Antitoxin over five years for delivery into the Strategic National Stockpile beginning in 2007.
Lasers and Dermatology
Medical lasers have been used for dermatology applications such as removal of port wine stains, dark spots, tattoos, acne scars and other blemishes for over a decade. Lasers are used for a growing number of cosmetic procedures including hair removal, treatment of wrinkles, and tooth whitening. For risk information on the specific laser treatment that you are considering, ask your physician or operator for the patient labeling for the laser device.
The popularity of laser hair removal has increasingly grown, prompting many laser manufacturers to conduct research and seek FDA clearance for their lasers for this indication. The market is growing so quickly that FDA cannot maintain an up-to-date list of all laser manufacturers whose devices have been cleared for hair removal, as this list continues to change. To learn if a specific manufacturer has received FDA clearance, you can check FDA’s Website at http://www.fda.gov/cdrh/databases.html under the 510(k) database. You will need to know the manufacturer or device name of the laser. You can also call FDA’s Center for Devices and Radiological Health, Consumer Staff, at 1-888-INFO-FDA or 301-827-3990, fax your request to 301-443-9535 or send an e-mail to: DSMICA@cdrh.fda.gov.
Manufacturers should be aware that receiving an FDA clearance for general permission to market their devices does not permit them to advertise the lasers for either hair removal or wrinkle treatment, even though hair removal or wrinkle treatment may be a by-product of any cleared laser procedure. Further, manufacturers may not claim that laser hair removal is either painless or permanent unless the FDA determines that there are sufficient data to demonstrate such results. Several manufacturers received FDA permission to claim, “permanent reduction,” NOT “permanent removal” for their lasers. This means that although laser treatments with these devices will permanently reduce the total number of body hairs, they will not result in a permanent removal of all hair. The specific claim granted is “intended to effect stable, long-term, or permanent reduction” through selective targeting of melanin in hair follicles. Permanent hair reduction is defined as the long-term, stable reduction in the number of hairs re-growing after a treatment regime, which may include several sessions. The number of hairs regrowing must be stable over time greater than the duration of the complete growth cycle of hair follicles, which varies from four to twelve months according to body location. Permanent hair reduction does not necessarily imply the elimination of all hairs in the treatment area.
FDA does not make comparisons between systems or how well or safely they work compared to another company’s system. FDA does not recommend one laser system over another. Lasers cleared for body hair removal are also cleared for facial hair removal.
Lasers are also being used to treat wrinkles. Several manufacturers have received FDA clearance to claim treatment of wrinkles, while others may claim skin resurfacing. Patients have reported reddening of the skin, which lasted from one to four months. Pain was mild and could be treated with over-the-counter analgesics. Consumers should bear in mind that skin abrasion, whether achieved by lasers, chemicals or abrasive materials, means removing one or more layers of skin, which can be painful and could cause redness, swelling or scarring, depending on how each person heals.
People considering this procedure should consult a dermatologist or the manufacturer to determine whether or not they would be good candidates. Be sure to ask your dermatologist for a copy of the patient labeling for the specific laser device used to understand the risks.