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Fungal Infections Associated with Lymphedema

For those of us with lymphedema, proper skin care is essential to our health and well being.

The skin must be cared for correctly and every effort must be made to avoid fungus and fungal infections. If after all we do, we acquire one, it must be treated promptly. These fungal infections can be catastrophic.

Types of Fungal Infections

Tinea, Athlete's Feet, Candida, Jock Itch, Yeast Infections, Oral thrush, Cryptococcosis, Sporotrichosis, Pityriasis Versicolor, Histoplasmosis, Blastomycosis, Tinea Pedis, Tinea Cruris, Tinea Corporis, Tinea Unguiuum, Tinea Barbae, Tinea Manuum, Tinea Capitis

Definition of a fungus

Member of a class of primitive vegetable organisms. These plants lack cholorphyll, are generally parasitic and reproduce by spores.

Fungus causing infections can be classified in two distinct groupings. Fungus infections from a mold-like fungi include athlete's feet, jock itch, ringwowrm and tinea capitis.

Fungus infections from a yeast-like fungi include diaper rash, oral thrush, cutaneous candida and some genital rashes.

Four Key Features of a Fungus

1.) Fungi are a kingdom consisting entirely of absorptive heterotrophs. In contrast to certain bacteria and autotrophic plants, they need pre-formed organic compounds as energy sources, and as carbon sources for cellular synthesis. Fungi characteristically live embedded in some form of food substrate where they absorb simple, soluble nutrients through the wall and cell membrane. In many cases, these simple nutrients may be released from more complex polymers by depolymerases that are secreted into the external medium. It is therefore unlikely that there is a substrate anywhere in the world that a fungus cannot utilize or benefit from. It should be noted the cell wall of the fungi prevents food being engulfed by phagocytosis.

2.) Fungi usually are filamentous, with the single filaments being termed hyphae. Fungal hyphae grow and branch to produce a network of filaments which constitutes the mycelium. The mycelium enlarges by extension of single hyphae which show polar growth, meaning they grow only at their extreme tips. This apical growth is in contrast to the intercalary growth of most other filamentous organisms. Expansion of the mycelium is continuous if the hyphae can keep on extending on the medium they are residing in. However, changes do take place as the mycelium ages and as that part of the food source on which it is growing is no longer able to provide sufficient nutrients. It should be noted here that though many fungi are hyphae in character, with an indeterminate mycelium capable of producing the largest of organisms, there are actually five major body forms in the kingdom.

3.) Fungi can reproduce by both asexual and sexual means. Reproduction is invariably connected to the production of spores, produced at specialized structures and fully equipped to start a new colony independent of the parent mycelium, and usually some distance from it. Fungal spores vary enormously in shape, size and other special properties, linked to their numerous roles in dispersal or survival.

4.) Fungi are all eukaryotic. This means they have a membrane-bound nucleus containing several chromosomes (unlike a circular strand of DNA found in prokaryotes), and a number of membrane-bound organelles including mitochondria and vacuoles. Eukaryotes also contain DNA that includes non-coding regions entitled introns, and ribosomes of the 80S type, contrary to the 70S type found in prokaryotes.

In summary, fungi are a kingdom of heterotrophic absorptive eukaryotes which probably arose from a choanoflagellate like protozoan by the origin of beta-glucan/chitin walls, with the simultaneous loss of phagotrophy. Multiple losses and origins of complex characters would have occurred since then, including major changes in wall chemistry, sometimes totally losing the whole vegetative wall. Fungi are ordinarily aerobic, having mitochondria with flat cristae and peroxisomes, the latter giving yeasts some of their chemical virtuosity. The 'true' fungi consist of the phyla Chytridiomycota, Zygomycota, Ascomycota and Basidiomycota, each sharing important morphological and biochemical features, such as walls typically containing chitin. Fungi are restricted to a monophyletic lineage, the closest relatives to these true fungi being the Choanoflagellates, a group ancestral to multicellular animals too. The true fungi display evident evolutionary trends with respect to their colony structure, ecological relationships, cell form, life cycle and sexuality.(1)

(1) World of Fungus

Types of Fungal infections

Types list: The list of types of Fungal infections mentioned in various sources includes:

Candida Vaginal Candidiasis Oral thrush Athlete's foot Tinea Yeast infections Ringworm - not a worm but a fungus. Cryptococcosis Sporotrichosis Pityriasis Versicolor

Types discussion: Mycoses can affect your skin, nails, body hair, internal organs such as the lungs, and body systems such as the nervous system. Aspergillus fumigatus, for example, can cause aspergillosis, a fungal infection in the respiratory system.

Some fungi have made our lives easier. Penicillin and other antibiotics, which kill harmful bacteria in our bodies, are made from fungi. Other fungi, like certain yeasts, also can be beneficial. For example, when a warm liquid like water and a food source are added to certain yeasts, the fungus ferments. The process of fermentation is essential for making healthy foods like some breads and cheeses.1

Acknowledgment and Thanks

Wrong Diagnosis

How Do I Know if I Have a Fungal Infection?

There are many skin problems that can look like a fungal infection so the best way to know for sure is to ask your doctor. However, there are some signs you can look for with the different types of fungal infections:

Athlete's foot has symptoms that include dry, cracked, and itchy skin between the toes. Some people also have red, scaly blisters on the bottoms and sides of their feet. There may also be a watery discharge from the blisters.

Jock itch appears as a rash with elevated edges. It too is itchy and often feels like it is burning. It's pretty common, especially if you play sports where you sweat and wear athletic equipment.

Ringworm of the head begins as a small pimple that becomes larger. The hair in the infected area can become brittle and break off, leaving scaly patches of baldness. But don't sweat it - it will grow back! If you have ringworm on your arms, legs, or chest, you may see small, red spots that grow into large rings.

Candida, the yeast-like fungus, causes the skin around the infected area to itch. The skin may also be red and swollen.

Prevention of Fungal Infections

Getting rid of a fungal infection is not all that difficult. Your doctor may decide to scrape a small amount of the irritated skin or clip off a piece of hair or nail and look at it under a microscope. Once your doctor knows what kind of infection you have, there are special antifungal creams and shampoos that can help to get rid of it. Sometimes the doctor will prescribe a medicine to take by mouth for many weeks. Make sure you take the medicine for as long as the doctor tells you.

Maybe fungal infections can't be avoided altogether, but there are some ways you can help yourself ward them off.

Walk away from athlete's foot by following these simple steps:

Wash your feet everyday.

Dry your feet completely, especially between your toes.

Wear sandals or shower shoes when walking around in locker rooms, public pools, and public showers.

Wear clean socks and if they get wet or damp, be sure to change them as soon as you can. Use a powder (talcum or antifungal) on your feet to help reduce perspiration.

You may love to play sports and not be able to avoid jock itch, but you can help to keep it away when you:

Wear clean, cotton underwear and loose-fitting pants.

Keep your groin area clean and dry.

Yeast infections can be avoided, too, if you:

Don't hang out in wet swimsuits; change as soon as possible. Wear clean, cotton underpants.

The truth is there may always be a “fungus among us,” but we can make it a lot tougher for them to invade and grow!

Reviewed by: Patrice Hyde, MD Date reviewed: November 2000

Acknowledgment and Thanks Kids Health What are the different types of fungal infection?

When it comes to human body, the term fungus refers to a type of germ that lives on all of us. This germ harmless most of the time, can cause problems occasionally. This is called a fungal infection. Persistent fungal infections may be indicators of an imbalance in the body's microflora (the small, usually bacterial, inhabitants of gut,skin surfaces and mucous membranes).

Fungal infections

diseases caused by organisms of the kingdom Fungi, which includes various genera that may cause disorders with musculoskeletal manifestations (Table 1). These pathogical conditions are discussed in more detail under their specific names.

Fungal infections, Table 1. Various types of fungal infections.

Disease Organism

Actinomycosis Actinomyces species

Nocardiosis Nocardia species

Cryptococcosis (torulosis) Cryptococcus neoformans

North American blastomycosis Blastomyces dermatitidis

South American blastomycosis (paracoccidioidomycosis) Blastomyces brasiliensis

Coccidioidomycosis Coccidioides immitis

Histoplasmosis Histoplasma capsulatum

Sporotrichosis Sporothrix schenkii

Candidiasis Candida albicans

Mucormycosis Mucor species

Aspergillosis Aspergillus species

Maduromycosis (mycetoma) Madurella,Nocardia, Streptomyces species

http://www.amershamhealth.com/medcyclopaedia/Volume%20III%201/FUNGAL%20INFECTIONS.asp

Tinea Infections

One of the main reasons people find tinea infections don't clear up is because they don't use their medicines long enough.

“Most tinea infections need treatment for one to two weeks or sometimes more, but they should also be treated for a minimum of one week after the infection has cleared,” recommend Self Care pharmacists.

Many people know they are suffering from a yeast infection, jock itch or athletes foot, but never really realized that these are all different types of fungal infections. Most fungal infections are commonly called tinea. You can get tinea infections on your body (for example ringworm, jock itch), or on your feet, nails or scalp.

Another tinea infection, called pityriasis versicolor, affects the skin on the trunk of the body, especially the back. It can also spread to the neck, arms or stomach. When people tan in summer the affected parts remain as whitish patches on their body and they may often wonder what this is.

There are also other fungal infections like oral thrush (in the mouth) or nappy rash.

Although fungal infections can occur at any time during the year, they tend to occur most frequently during the warm summer months.

Fungal infections are caused by organisms called fungi and the heat of the warmer weather gives the fungi ideal conditions to grow. Fungal infections tend to develop where two skin surfaces come together such as between toes, the buttocks and under the breasts in women. These areas tend to be moister because they sweat a lot or they are not dried well enough after a shower or bath.

A very common fungal infection is athletes foot, also called tinea pedis. You don't have to be an athlete to get athletes foot. Athletes foot occurs most frequently in warm conditions, when the feet sweat a lot and don't get a lot of air circulation.

Athletes foot can be caught by sharing public showers or walking barefoot in these places. The infection usually starts around the fourth and fifth toes where the skin can become soft and whitish in colour and start to flake. The infection is often very itchy.

All fungal infections can be treated with medicines from your pharmacy. Treatments are available as creams, lotions, solutions, oral liquids for mouth thrush, powders or sprays. Your Self Care pharmacist can suggest the best treatment for your needs.

“However you must use your anti-fungal medicines until the infections has cleared,” advise Self Care pharmacists. “To prevent the infection from coming back you should also use it for at least another week or so after it clears.”

Nail and scalp fungal infections need stronger medicines, which your doctor can prescribe and you may need to use the medicines for a much longer time.

Fungus Infections: Preventing Recurrence

Doctors have excellent treatments for skin fungus infections that occur on the feet, nails, groin, hands and other locations. Unfortunately, there is a strong tendency for fungal infections to recur in many people even after effective clearing with medication. This is because we all have our strengths and weaknesses. Some people are prone to allergies. Others get lots of colds. Others get stomach ulcers. And some people are prone to recurrent skin fungus infections.

The tendency for fungus to recur in many adults, especially on the feet and toenails, is a genetic condition. Their skin cannot recognize the fungus as foreign and get rid of it. After having a fungus there for a while the body's immune system learns to live with the fungus and no longer tries to get rid of it.

Children only rarely get fungal infections of the feet, especially before the age of five. Their bodies still react vigorously to the fungus. For some reason, they are more likely to get it on the scalp than adults are.

Fungus is all around us, on floors, in dirt, and on other people. It is hard to avoid forever. It likes warmth and moisture, making certain parts of the skin more vulnerable. A fungus is a superficial skin problem, not an internal one. It does not spread by going inside the body. Cortisone creams, tried by many patients, help fungus grow! The rash may get less red and itchy at first, but spreads out and recurs, itchier than ever, when the cortisone is stopped.

A fungus sheds “spores”, like tiny seeds, which wait for the right moment to grow into new fungus. The most common place for these spores to collect is in shoes. Therefore, after effective treatment, a fungus may recur quickly where spores are present. Fungus doesn't care what color the socks are. White socks offer no advantage. Absorbent cotton or wool socks are best.

Some Rules for Prevention: Remember, nothing works one hundred per cent. Try combinations of these ideas.

1. Use the medicine completely and as recommended. The fungus may till be present long after it is no longer visible as a rash.

2. Keep feet clean, cool and dry. Change socks. Wear shoes that “breathe” like leather, rather than plastic.

3. Make sure shoes fit correctly and are not too tight.

4. Apply an anti-fungal cream, like Lotrimin or Lamisil, or a prescription antifungal cream to the bottom of the feet, and on the nails, about twice a week. This may help prevent early re-growth of the fungus. In some cases, an oral medication may be prescribed.

5. Avoid walking barefoot, especially in bathrooms, locker rooms, gyms, on carpeting, and in public bathing areas. Wear slippers or stand on a towel or piece of paper.

6. Keep toenails short, cut straight across and avoid ingrown nails. Do not use the same clippers on abnormal nails and normal nails.

7. Family members and close personal contacts should treat any fungus infections they may have to avoid trading back and forth.

8. Apply an anti-fungal powder, like Zeasorb-AF to the shoes every day, to keep spores from growing.

9. Discard old shoes, boots, slippers and sneakers. Do not share footwear with others.

10.If one has had a body fungus, in the groin or elsewhere on the skin, consider using an anti-dandruff shampoo, like Selsun Blue on this area twice a month. Lather up and leave it on the skin for about five minutes, then wash off completely. In some cases a preventive medication may be prescribed.

http://www.aocd.org/skin/dermatologic_diseases/fungus_preventing.html

What are fungal infections of the nails?

Fungal infections of the nails are common. The fungus grows in the nail bed, where the nail meets the skin. The fungus grows slowly and does not spread to internal organs. The main concern is the nail discoloration (usually yellow) and change in nail texture and growth. Nails can become crumbly, break easily, and grow irregularly. But because other nail conditions can mimic fungal infection, most doctors will confirm the diagnosis by sending a nail clipping for laboratory evaluation – especially if treatment is being considered.

Fungal infections are not commonly contagious or spread easily between people. The fungus grows in people whose bodies “allow” the fungus to become established without mounting an immune response to suppress the fungus. We know of no ways to boost your immune system to make fungal infections less likely. You may be able to prevent fungus infections by:

Keeping your feet dry, avoiding constant moisture

Avoid non porous, closed shoes made of synthetic materials

Wearing absorbent socks

Wearing water proof sandals when in public showers

What can be done about fungal nail infection?

Because the fungus grows slowly, it is hard to eliminate. The anti fungal medications that eliminate the fungus are strong, must be taken by mouth, and must be taken conscientiously for months in order to be effective. Each drug has potential side effects on other body organs (especially the liver, skin, or bone marrow). To monitor for side effects, periodic blood testing must be obtained, usually monthly, during the time you take the medication. Any symptoms suggesting organ damage should be reported immediately to your physician, such as: unusual fatigue, severe loss of appetite, nausea, yellow eyes, dark urine, pale stool, skin rashes, bleeding, enlarged lymph glands, or signs of infection.

Unfortunately, anti fungal creams applied directly to the nail cannot penetrate the nail bed to kill the fungus at its source, so they are not usually effective.

How effective are the medications at curing the fungus?

The anti fungal medications usually suppress the nail infection when taken as directed. Unfortunately, they cannot guarantee permanent cure. At least 1 in 5 patients (20%) and probably more will have a recurrence of the original nail infection at some time, and re-treatment with medication would be necessary.

Should I take medication to treat my fungal nail infection?

Doctors usually recommend treating fungal nail infections only when such infections cause secondary problems, like pain, recurring ingrown toenails, or secondary bacterial infections of the nails or skin. If the nail infection causes no symptoms, then doctors often will discourage treatment because of the potential side effects, the need to monitor the blood throughout therapy, and the high recurrence rate. Patients with liver or heart disease generally should not take these medications.

Some insurance companies require documentation of secondary problems beyond the mere presence of the fungal infection before they will cover the costs of the anti fungal medications.

April 2002

Acknowledgment and Thanks

Palo Alto Medical Foundation

Ringworm

Ringworm is a contagious fungus infection that can affect the scalp, the body, the feet (athlete's foot), or the nails.

People can get Ringworm from: 1) direct skin-to-skin contact with an infected person or pet, 2) indirect contact with an object or surface that an infected person or pet has touched, or 3) rarely, by contact with soil.

Ringworm can be treated with fungus-killing medicine. To prevent Ringworm, 1) make sure all infected persons and pets get appropriate treatment, 2) avoid contact with infected persons and pets, 3) do not share personal items, and 4) keep common-use areas clean.

What is Ringworm?

Ringworm is a contagious fungus infection that can affect the scalp, the body (particularly the groin), the feet, and the nails. Despite its name, it has nothing to do with worms. The name comes from the characteristic red ring that can appear on an infected person's skin. Ringworm is also called Tinea.

What is the infectious agent that causes Ringworm?

Ringworm is caused by several different fungus organisms that all belong to a group called “Dermatophytes.” Different Dermatophytes affect different parts of the body and cause the various types of Ringworm:

Ringworm of the scalp Ringworm of the body Ringworm of the foot (athlete's foot) Ringworm of the nails

Where is Ringworm found?

Ringworm is widespread around the world and in the United States. The fungus that causes scalp Ringworm lives in humans and animals. The fungus that causes Ringworm of the body lives in humans, animals, and soil. The fungi that cause Ringworm of the foot and Ringworm of the nails live only in humans.

How do people get Ringworm?

Ringworm is spread by either direct or indirect contact. People can get Ringworm by direct skin-to-skin contact with an infected person or pet. People can also get Ringworm indirectly by contact with objects or surfaces that an infected person or pet has touched, such as hats, combs, brushes, bed linens, stuffed animals, telephones, gym mats, and shower stalls. In rare cases Ringworm can be spread by contact with soil.

What are the signs and symptoms of Ringworm?

Ringworm of the scalp usually begins as a small pimple that becomes larger, leaving scaly patches of temporary baldness. Infected hairs become brittle and break off easily. Yellowish crusty areas sometimes develop.

Ringworm of the body shows up as a flat, round patch anywhere on the skin except for the scalp and feet. The groin is a common area of infection (groin Ringworm). As the rash gradually expands, its center clears to produce a ring. More than one patch might appear, and the patches can overlap. The area is sometimes itchy.

Ringworm of the foot is also called athlete's foot. It appears as a scaling or cracking of the skin, especially between the toes.

Ringworm of the nails causes the affected nails to become thicker, discolored, and brittle, or to become chalky and disintegrate.

How soon after exposure do symptoms appear?

Scalp Ringworm usually appears 10 to 14 days after contact, and Ringworm of the skin 4 to 10 days after contact. The time between exposure and symptoms is not known for the other types of Ringworm.

How is Ringworm diagnosed?

A health-care provider can diagnose Ringworm by examining the site of infection with special tests.

Who is at risk for Ringworm?

Anyone can get Ringworm. Scalp Ringworm often strikes young children; outbreaks have been recognized in schools, day-care centers, and infant nurseries. School athletes are at risk for scalp Ringworm, Ringworm of the body, and foot Ringworm; there have been outbreaks among high school wrestling teams. Children with young pets are at increased risk for Ringworm of the body.

What is the treatment for Ringworm?

Ringworm can be treated with fungus-killing medicine. The medicine can be in taken in tablet or liquid form by mouth or as a cream applied directly to the affected area.

What complications can result from Ringworm?

Lack of or inadequate treatment can result in an infection that will not clear up.

Is Ringworm an emerging infection?

Although Ringworm is not tracked by health authorities, infections appear to be increasing steadily, especially among pre-school and school-age children. Early recognition and treatment are needed to slow the spread of infection and to prevent re-infection.

How can Ringworm be prevented?

Ringworm is difficult to prevent. The fungus is very common, and it is contagious even before symptoms appear.

Steps to prevent infection include the following:

Educate the public, especially parents, about the risk of Ringworm from infected persons and pets.

Keep common-use areas clean, especially in schools, day-care centers, gyms, and locker rooms. Disinfect sleeping mats and gym mats after each use.

Do not share clothing, towels, hair brushes, or other personal items.

Infected persons should follow these steps to keep the infection from spreading:

Complete treatment as instructed, even after symptoms disappear. Do not share towels, hats, clothing, or other personal items with others.

Minimize close contact with others until treated. Make sure the person or animal that was the source of infection gets treated.

This fact sheet is for information only and is not meant to be used for self-diagnosis or as a substitute for consultation with a health-care provider. If you have any questions about the disease described above or think that you might have a fungus infection, consult a health-care provider.

http://www.astdhpphe.org/infect/ringworm.html

Oral Thrush

What is oral thrush?

Oral thrush in an adult.

Oral thrush is an infection of yeast fungus, Candida albicans, in the mucous membranes of the mouth. Strictly speaking, thrush is only a temporary candida infection in the oral cavity of babies. However, we have for this purpose expanded the term to include candida infections occurring in the mouth and throat of adults, also known as candidosis or moniliasis.

How do you get oral thrush?

Candida is present in the oral cavity of almost half of the population. Everyone who wears dentures will have candida, without necessarily suffering any ill effects.

Candida does not become a problem until there is a change in the chemistry of the oral cavity that favours candida over the other micro-organisms that are present.

These changes can occur as a side effect of taking antibiotics or drug treatment such as chemotherapy. These changes can also be caused by certain conditions such as diabetes, drug abuse, malnutrition, and as a consequence of immune deficiencies relating to old age or infection, such as AIDS.

Furthermore, people whose dentures don't fit well can sustain breaks in the mucous membranes in their mouth, which can act as a gateway for candida. People who suffer from this problem often have moist, pale pink spots on their lips, known as angular cheilitis, which is an indication of a candida infection.

What are the symptoms of oral thrush?

White, cream coloured, or yellow spots in the mouth. The spots are slightly raised. There is normally no pain in the area underneath the spots. If you scrape off these spots, they leave small wounds that bleed slightly. In adults, thrush can cause an uncomfortable burning sensation in the mouth and throat.

Who is at special risk?

Newborn babies.

Denture users.

Adults with diabetes or other metabolic disturbance.

People undergoing antibiotic or chemotherapy treatment.

Drug users.

People with poor nutrition.

People with an immune deficiency.

How does the doctor diagnose oral thrush?

In babies, thrush is usually diagnosed on the basis of the clinical picture. Occasionally, in order to make a diagnosis, the doctor will scrape the baby's tongue and send the sample for analysis.

In adults, many other diseases and illnesses, including very early stages of cancer, can have similar symptoms. Therefore it is important to consult your doctor and get a thorough check-up.

In cases where thrush occurs as the result of disease or illness in other organs or systems, like AIDS, sudden and very intense thrush can be a sign of a general aggravation of the main illness. This makes it all the more important to pay attention to this and similar changes, so you can get help in time.

How is oral thrush treated?

Firstly, the condition that caused the thrush must be brought under control. This might involve investing in new and better fitting dentures, or adjusting diabetes treatment. For AIDS patients, it is not always possible to correct the immune deficiency, and a course of oral treatment using antifungal drugs has to be used.

Once the condition that caused the oral thrush has been treated, the thrush itself can be cured. Treatment is with antifungal medicines such as nystatin, amphotericin or miconazole in the form of pastilles that are sucked or oral suspensions that are held in the mouth before swallowing. These allow the antifungal agent to act locally in the mouth.

In certain complicated cases, or if the infection spreads, systemic treatment will be necessary in the form of antifungal tablets, or perhaps in the form of injections.

Coping with the symptoms of oral thrush

Thrush can make the mouth so sensitive that it is impossible to perform regular oral hygiene. Use a very soft toothbrush. It can often help to rinse the mouth with a diluted solution of 3 per cent hydrogen peroxide.

Outlook

If whatever caused the thrush can be brought under control, the infection is likely to go away after a few days of treatment with a fungicide.

Based on a text by Dr Flemming Andersen and Ulla Søderberg, specialist

Last updated 01.02.2002

Ackowledgment and Thanks

Net Doctor.co.uk

Cryptococcal meningitis

Cryptococcal meningitis is a very serious fungal infection. It is caused by a fungus found mainly in dirt and bird droppings. Meningitis means swelling of the meninges. The meninges cover the brain and spinal cord. Symptoms can be hard to recognize as being caused by cryptococcal infection. Watch for fever, vomiting, headache, nausea, fatigue, loss of appetite, and a general feeling of not being well. Other symptoms are a stiff neck and, infrequently, seizures. Pneumonia can be an early sign of infection. Tell your doctor about symptoms right away.

A common treatment for this condition is amphotericin B, which must be given by intravenous injection. A new treatment that can be given by pill, in some cases, or by intravenous injection is Flucanozole, or Diflucan. Most people prefer this treatment because it causes few side effects.

Histoplasmosis

Histoplasmosis can be a life-threatening fungal infection and commonly occurs in the Southwestern U.S. In the past, histoplasmosis was treatable only with intravenous amphotericin. Itraconazole is used today, although it may not be effective for treating histoplasmosis involving the central nervous system and brain, since it does not penetrate well into the cerebrospinal fluid, which is the fluid that surrounds the spinal cord and brain.

histoplasmosis2.jpg

Blastomycosis

Blastomycosis is a fungal infection involving the lungs and occasionally spreading to the skin. The fungus is of unknown natural source. Most reported cases are from the southeastern states and the Mississippi River valley, and occur in men ages 20 to 40. When infection occurs in the lungs, a dry hacking or productive cough, chest pain, fever, chills, drenching sweats, and shortness of breath are initial symptoms. If untreated, the disease slowly causes death. Amphotericin B is highly effective. Improvement begins within a week, with rapid disappearance of organisms.

http://www.aegis.com/factshts/network/simple/fungal.html

Treating Onychomycosis

PHILLIP RODGERS, M.D., and MARY BASSLER, M.D. University of Michigan Medical School, Ann Arbor, Michigan

Onychomycosis accounts for one third of fungal skin infections. Because only about one half of nail dystrophies are caused by fungus, the diagnosis should be confirmed by potassium hydroxide preparation, culture or histology before treatment is started. Newer, more effective antifungal agents have made treating onychomycosis easier. Terbinafine and itraconazole are the therapeutic agents of choice. Although the U.S. Food and Drug Administration has not labeled fluconazole for the treatment of onychomycosis, early efficacy data are promising. Continuous oral terbinafine therapy is most effective against dermatophytes, which are responsible for the majority of onychomycosis cases. Intermittent pulse dosing with itraconazole is as safe and effective as short-term continuous therapy but more economical and convenient. With careful monitoring, patients treated with the newer antifungal agents have a good chance of achieving relief from onychomycosis and its complications. (Am Fam Physician 2001;63:663-72,677-8.)

Onychomycosis (tinea unguium) is a fungal infection of the nail bed, matrix or plate. Toenails are affected more often than fingernails.1,2 Onychomycosis accounts for one third of integumentary fungal infections and one half of all nail disease.1 Tinea unguium occurs primarily in adults, most commonly after 60 years of age. The incidence of this infection is probably much higher than the reported 2 to 14 percent.1 Occlusive footwear, locker room exposure and the dissemination of different strains of fungus worldwide have contributed to the increased incidence of onychomycosis.3

Tinea unguium is more than a cosmetic problem, although persons with this infection are often embarrassed about their nail disfigurement. Because it can sometimes limit mobility, onychomycosis may indirectly decrease peripheral circulation, thereby worsening conditions such as venous stasis and diabetic foot ulcers.4 Fungal infections of the nails can also be spread to other areas of the body and, perhaps, to other persons. Dermatophytes, yeasts and nondermatophytic molds can infect the nails.1 The clinical significance of molds is uncertain, because they may be colonizing organisms that are not truly pathogenic.3,5

Classification of Onychomycosis

Distal Subungual Onychomycosis

The most common form of tinea unguium is distal subungual onychomycosis, which can also be distal and lateral (Figures 1 and 2). Distal subungual onychomycosis may develop in the toenails, fingernails or both. Some degree of tinea pedis is almost always present. The infection is usually caused by Trichophyton rubrum, which invades the nail bed and the underside of the nail plate, beginning at the hyponychium and then migrating proximally through the underlying nail matrix2,3 (Figure 3). Susceptibility to distal superficial onychomycosis may occur in an autosomal dominant pattern within families.1

White Superficial Onychomycosis

White superficial onychomycosis accounts for only 10 percent of onychomycosis cases.3 The toenails are usually affected (Figure 4). White superficial onychomycosis is caused by certain fungi that directly invade the superficial layers of the nail plate and form well-delineated opaque “white islands” on the plate. As the disease progresses, these patches coalesce to involve the entire nail plate. The nail becomes rough, soft and crumbly. The most common causative agent is Trichophyton mentagrophytes.

Proximal Subungual Onychomycosis

Proximal subungual onychomycosis is the least common form of tinea unguium in healthy persons (Figure 5). It occurs when the infecting organism, usually T. rubrum, invades the nail unit through the proximal nail fold, penetrates the newly formed nail plate and then migrates distally. Fingernails and toenails are equally affected.1 This form of onychomycosis usually occurs in immunocompromised persons and is considered a clinical marker of human immunodeficiency virus infection.1 Proximal subungual onychomycosis can also arise secondary to local trauma.1-3

Candidal Onychomycosis

Patients with chronic mucocutaneous candidiasis may develop candidal infection of the nails. Candida species may invade nails previously damaged by infection or trauma.1,3 Candidal paronychia more commonly affects the hands and usually occurs in persons who frequently immerse their hands in water.5

Total Dystrophic Onychomycosis

Total dystrophic onychomycosis may be the end result of any of the four main forms of onychomycosis. This condition is characterized by total destruction of the nail plate.3

Diagnosis

Because fungi are responsible for only about one half of nail dystrophies, the diagnosis of onychomycosis may need to be confirmed by potassium hydroxide (KOH) preparation, culture or histology. Psoriasis, lichen planus, contact dermatitis, trauma, nail bed tumor and yellow nail syndrome may be mistakenly diagnosed as onychomycosis.1,2 A fungal etiology is unlikely if all fingernail or toenails are dystrophic.3

Obtaining a Specimen

The technique used to collect specimens depends on the site of the infection.1,3 In distal subungual onychomycosis, the concentration of fungus is greatest in the nail bed. Therefore, the nail should be clipped short, and a small curette or number-15 scalpel blade should be used to obtain a specimen from the nail bed as close to the cuticle as possible. A specimen should also be taken from the underside of the nail plate. In white superficial onychomycosis, a number-15 blade or curette can be used to scrape the nail surface or the white area, and remove infected debris.

In proximal superficial onychomycosis, the healthy nail plate should be gently pared away with a number-15 scalpel blade. A sharp curette can be used to remove material from the infected proximal nail bed as close to the lunula as possible.

In candidal onychomycosis, infected material should be collected from the proximal and lateral nail edges.

Treatment

Historically, the treatment of onychomycosis has been challenging. Orally administered griseofulvin (Grisactin, Gris-Peg) has been available for many years, but its use is limited by a narrow spectrum, the necessity for long courses of treatment and high relapse rates. The oral form of ketoconazole (Nizoral) is much more effective but carries a risk of hepatotoxicity.6

Onychomycosis has long been treated with topical antifungal preparations. However, these agents are inconvenient to use, and results are often disappointing. Treatment using nail avulsion in combination with topical therapy has been somewhat more successful, but this approach can be time-consuming, temporarily disabling and painful. The U.S. Food and Drug Administration (FDA) has labeled ciclopirox (Penlac) nail lacquer for the treatment of mild to moderate onychomycosis caused by T. rubrum without involvement of the lunula. Although safe and relatively inexpensive, ciclopirox therapy is seldom effective.7

In recent years, treatment outcomes in patients with onychomycosis have improved substantially, primarily because of the introduction of more effective oral antifungal medications.8 Current evidence supports the use of these newer agents as part of individualized treatment plans that consider patient profiles, nail characteristics, infecting organism(s), potential drug toxicities and interactions, and adjuvant treatments.9

Triazole and allylamine antifungal drugs have largely replaced griseofulvin and ketoconazole as first-line medications in the treatment of onychomycosis. These agents offer shorter treatment courses, higher cure rates and fewer relapses.10 Of the newer drugs, terbinafine (Lamisil) and itraconazole (Sporanox) are the most widely used, with fluconazole (Diflucan) rapidly gaining acceptance. These medications share characteristics that enhance their effectiveness: prompt penetration of the nail and nail bed,3,11 persistence in the nail for months after discontinuation of therapy12,13 and generally good safety profiles. Published studies measuring “mycologic cure” (negative KOH preparation or negative cultures) and “clinical cure” (normal nail morphology) have demonstrated the effectiveness of all three medications.

Terbinafine

Terbinafine is an allylamine antifungal agent that is active against dermatophytes, which are responsible for the majority of onychomycosis cases. This agent is notably less effective against nondermatophytes, including Candida species and molds.

Adverse effects, including headache, rash and gastrointestinal upset, are reported more often with terbinafine than with placebo. Yet these side effects are uncommon and resolve with discontinuation of the drug.14 Because of its hepatic metabolism, terbinafine has several important drug interactions (Table 1).15-17

Rare but serious complications, such as cholestatic hepatitis, blood dyscrasias and Stevens-Johnson syndrome, have been reported in patients treated with terbinafine. Consequently, liver enzyme levels and a complete blood count (including a platelet count) should be obtained before terbinafine is initiated and repeated every four to six weeks during treatment.18 Terbinafine should be discontinued if the aspartate aminotransferase or alanine aminotransferase level becomes elevated to two or more times normal.

The FDA-labeled dosage of terbinafine is 250 mg per day given continuously for 12 weeks to treat toenail infections and for six weeks to treat fingernail infections. Studies have shown that the regimen for toenails results in a mycologic cure rate of 71 to 82 percent and a clinical cure rate of 60 to 70 percent.19,20 Shorter courses and pulse dosing of terbinafine have shown promise in small studies, but data are not yet sufficient to support the use of these regimens.21

Itraconazole

Itraconazole is a newer triazole medication with a broad antifungal spectrum that includes dermatophytes, many nondermatophytic molds and Candida species. Headache, rash and gastrointestinal upset occur in about 7 percent of treated patients, but hepatic toxicity is rare.22

Because itraconazole is metabolized by the hepatic cytochrome P450 system, significant drug interactions can occur (Table 1).15-17 Notably, concurrent use with quinidines and pimozide (Orap) is contraindicated because of the risk of ventricular arrhythmias. Itraconazole is also contraindicated for concomitant use with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, such as atorvastatin (Lipitor), because of the increased risk of rhabdomyolysis. In addition, itraconazole should not be taken with some benzodiazepines, such as midazolam (Versed) and triazolam (Halcion), because of exaggerated sedation and potential airway compromise.15

Increased gastric pH decreases the absorption of itraconazole. Therefore, the effectiveness of this antifungal agent can be decreased by histamine H2 blockers such as ranitidine (Zantac) and famotidine (Pepcid), and by proton pump inhibitors such as omeprazole (Prilosec) and lansoprazole (Prevacid). For this reason, itraconazole should be taken with food.

The FDA-labeled dosage of itraconazole is 200 mg once daily taken continuously for 12 weeks to treat toenail infections and for six weeks to treat fingernail infections. The FDA has labeled pulse therapy only for the treatment of fingernail infections. Pulse treatment consists of 200 mg taken twice daily for one week per month, with the treatment repeated for two to three months (i.e., two to three “pulses”).7,8,22,23 This dosage, given in three to four pulses, has also been shown to be effective in the treatment of toenail infections.7,8,22,23 Published studies have demonstrated similar success rates for continuous and pulse therapies, with mycologic cure rates ranging from 45 to 70 percent and clinical cure rates ranging from 35 to 80 percent.22,24,25 Liver enzyme monitoring is recommended before continuous therapy is initiated and every four to six weeks during treatment. No monitoring recommendation is given for pulse therapy.26

Fluconazole

Like itraconazole, fluconazole is active against common dermatophytes, Candida species and some nondermatophytic molds. Adverse effects, including nausea, headache, pruritus and liver enzyme abnormalities, are reported in approximately 5 percent of treated patients.26 These side effects remit after the discontinuation of fluconazole. The absorption of this drug is not pH sensitive and is not affected by acid suppression or food intake. However, fluconazole has important drug interactions15 (Table 1).15-17

Fluconazole is not currently labeled by the FDA for the treatment of onychomycosis, but early efficacy data are promising.13,27,28 Attention has focused on once-weekly dosing (450 mg), taking advantage of the drug's pharmacokinetics to reduce treatment costs, decrease rates of adverse effects and potentially improve compliance. In one placebo-controlled study involving patients with fingernail onychomycosis,29 fluconazole in a dosage of 450 mg taken once weekly for three months was associated with a 90 percent clinical cure rate and nearly total mycologic eradication. Lower dosages were slightly less effective. No differences in complication rates were observed between the treatment and placebo groups. Published outcomes data27,28 on the use of fluconazole in toenail fungal infections demonstrated “clinical improvement” (i.e., less than 25 percent of the nail still affected) rates of 72 to 89 percent, compared with 3 percent for placebo.27 Treatment duration in these studies varied from four to nine months, with a small but measurable advantage shown for longer courses.27-29

Comparative Clinical Trials

Much of the published data on the treatment of onychomycosis are of limited clinical use. Many studies have been small and observational, and they have lacked randomization and control subjects. Recently, however, the results of a handful of larger randomized, controlled trials have been published. These studies provide more convincing guidance in choosing appropriate therapy.

In a 1998 study30 of 378 patients with dermatophytic onychomycosis, continuous terbinafine therapy was shown to be more effective than continuous itraconazole therapy in patients with toenail onychomycosis. Intention-to-treat analysis showed nearly 85 percent negative cultures in the treatment group compared with 55 percent in the placebo group, and 65 percent clinical improvement in the terbinafine group compared with 37 percent in the itraconazole group.

Other studies comparing terbinafine and itraconazole had similar findings.31,32 A recent prospective, double-blind, randomized, controlled trial33 compared the use of continuous terbinafine therapy and pulsed itraconazole therapy in 496 patients with toenail fungal infection. This well-designed study showed that terbinafine provided superior clinical and mycologic outcomes up to 15 months after treatment. To date, fluconazole has not been included in published direct-comparison trials.

Most patients in the published studies were infected with dermatophytes, against which terbinafine is most effective. Outcomes data for the treatment of nondermatophytic and candidal onychomycosis are limited, but broader spectrum triazole medications may be more effective against these pathogens.

Cost

Onychomycosis is expensive to treat. Costs include medications, procedures, laboratory tests and health care providers' time, as well as expenses associated with the management of adverse drug effects and treatment failures. One pharmacoeconomic study34 compared the cost-effectiveness of continuously dosed terbinafine and itraconazole in the treatment of toenail onychomycosis.34 The investigators concluded that continuous terbinafine therapy is less expensive, at a little over one half the price of continuous itraconazole treatment. It should be noted, however, that itraconazole pulse therapy is less expensive than continuous treatment (lower overall drug cost and no need for blood monitoring). Furthermore, the pharmacoeconomic study used national reference pricing and wholesale drug costs. Local laboratory standards, retail pharmacy costs and increasingly common payor formulary considerations may significantly alter individual costs.

Adjuvant Treatments

In addition to oral medications, some patients benefit from other treatments. Surgical or chemical nail avulsion may be useful in patients with severe onycholysis, extensive nail thickening or longitudinal streaks or “spikes” in the nail. These nail changes can be caused by a granulated nidus of infection (dermatophytoma), which responds poorly to standard courses of medical therapy.35,36

Longer courses of antifungal therapy may be useful in patients whose nails grow slowly, who have diminished blood supply to the nail bed as a result of conditions such as peripheral vascular occlusion or diabetes mellitus, or who have total or nearly total nail plate involvement.9

Topical antifungal creams or powders may also be beneficial, especially in patients with concomitant tinea pedis. To improve treatment outcomes and prevent recurrence, patients should be counseled about proper foot hygiene (Table 3). Patients should be encouraged to wear breathable footwear and 100 percent cotton socks when possible. They should be advised to keep their feet dry throughout the day. Similar infection patterns observed in households and patrons of communal bathing facilities suggest a role for foot protection in high-risk areas.21

Treatment Failure and Relapse

Rates of treatment failure can be extracted from published trials, but data on relapse are less readily available. Post-treatment follow-up is long, drop-out rates in many studies are significant or unreported, and most studies have not allowed crossover of treatment regimens. Furthermore, especially in outcomes of clinical improvement (as opposed to cure or fully normal nail appearance), evaluation criteria have not been standardized and often include subjective assessments that are difficult to quantify. Published studies have not specifically addressed the management of treatment failures or relapse.

Despite these difficulties, several measures may be helpful in managing unsuccessful treatment or relapse. The first step is to confirm mycology. If the initial diagnosis was based on a KOH preparation alone, culture of properly collected specimens is mandatory. Culture reports often identify multiple organisms, including possibly nonpathogenic molds, and treatment should be directed at the organism(s) most likely to be causative. A microbiology or infectious disease consultation may be valuable in interpreting the culture report.

Of note, there has been some concern about evolving drug resistance among fungal pathogens, particularly with the widespread use of systemic fluconazole therapy to treat oropharyngeal and recurrent vaginal candidiasis.5 However, the impact of antifungal resistance on the treatment of onychomycosis is not yet clear.

Careful clinical review may identify patient or nail characteristics that are impeding treatment. These factors can be addressed with appropriate medication changes or adjuvant measures. Because of superior efficacy, continuous antifungal therapy may be considered in patients who fail or relapse after pulse therapy.

Onychomycosis in Children

Onychomycosis in children is rare, with an estimated prevalence of 0.2 percent.38 Most often, onychomycosis develops in children with immunosuppression (e.g., acquired immunodeficiency syndrome, chemotherapy, congenital immunodeficiency syndromes), a strong familial history of onychomycosis or extensive cutaneous mycosis (tinea capitis or pedis).

Although griseofulvin remains the mainstay of onychomycosis treatment in children, the efficacy of this drug is variable, and relapse is common. Newly available medications may improve the traditionally mediocre treatment outcomes in this age group.

The FDA has not yet labeled terbinafine for use in children. However, some studies have shown terbinafine to be safe and quite effective in the treatment of tinea capitis, and it is licensed for this purpose in several countries.39 In more limited trials, itraconazole has also been shown to be safe and efficacious in the treatment of tinea capitis.21 If the safety and effectiveness of terbinafine and itraconazole are established over the longer courses needed to treat nail infections, they may become potent first-line therapies for onychomycosis in children.

The authors thank Barbara Apgar, M.D., M.S., and Stephen A. Swisher, M.D., University of Michigan Medical School, Ann Arbor, for their guidance and support.

Figures 1, 2, 4 and 5 were supplied by James E. Rasmussen, M.D., professor of dermatology and pediatrics, University of Michigan Medical School, Ann Arbor.

Members of various medical faculties develop articles for “Practical Therapeutics.” This article is one in a series coordinated by the Department of Family Medicine at the University of Michigan Medical School, Ann Arbor. Guest editor of the series is Barbara S. Apgar, M.D., M.S., who is also an associate editor of AFP.

This is a corrected version of the article that appeared in print.

The Authors

PHILLIP RODGERS, M.D.,

is clinical instructor in the Department of Family Medicine at the University of Michigan Medical School, Ann Arbor. Dr. Rodgers graduated from the Medical College of Ohio, Toledo, and completed a family practice residency at the University of Michigan Medical School.

MARY BASSLER, M.D., is clinical instructor in the Department of Family Medicine at the University of Michigan Medical School. Dr. Bassler graduated from Saint Louis University School of Medicine, St. Louis, and completed a family practice residency at Santa Monica (Calif.) Hospital.

Address correspondence to Phillip Rodgers, M.D., Briarwood Family Practice, University of Michigan Health System, 1801 Briarwood Circle, Ann Arbor, MI 48108 (e-mail: prodgers@umich.edu). Reprints are not available from the authors.

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Fungal infections in humans include: Aspergillosis, Blastomycosis, Candidiasis, Coccidioidomycosis, Cryptococcosis, Histoplasmosis, Paracoccidiomycosis, Sporotrichosis, Zygomycosis, Chromoblastomycosis, Eye Infections, Lobomycosis, Mycetoma, Otomycosis, Phaeohyphomycosis, Rhinosporidiosis, and Nail, Hair, and Skin disease (such as: Onychomycosis (Tinea unguium), Piedra, Pityriasis versicolor, Tinea barbae, Tinea capitis, Tinea corporis, Tinea cruris, Tinea favosa, Tinea nigra, and Tinea pedis).

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