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Eosinophilic pustular folliculitis

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Related Terms
  • Antiretroviral therapy, ART, classic EPF, Demodex, eosinophilic folliculitis, eosinophilic inflammation, eosinophilic pustular dermatosis, eosinophilic pustular folliculitis, eosinophils, follicle, HAART, hair follicle, hair follicle mite, highly active antiretroviral activity, HIV, human immunodeficiency virus, immune system, immunocompromised, immunodeficiency, inflammation, lymphocytic inflammation, Malassezia, mite, Ofuji's disease, pruritis, pustulosis, sebaceous gland cell, sebum oils, skin biopsy, sterile eosinophlic pustulosis.

Background
  • Eosinophilic pustular folliculitis (EPF) is a recurrent skin disorder that causes bumps and/or pimples to form near hair follicles. Clumps of white blood cells called eosinophils form these skin abnormalities. While the condition is not life threatening, it may cause intense itching.
  • There are three types of EPF: the classic EPF (Ofuji disease), HIV-associated EPF, and infantile EPF. All three types cause papulopustules or white-headed pimples that are filled with pus to form around hair follicles near the head and trunk. Patients also suffer from dry, scaly skin on the head and trunk that may be itchy or tender. Because little is known about the disease, it is unclear whether these three conditions are interrelated forms of a single disease, or if they are three different diseases.
  • Classic EPF mainly occurs in Japanese people living in Japan. While the exact incidence of classic EPF remains unknown, it is considered an uncommon disorder. Most individuals who have the classic form of the disease develop the condition when they are 20 to 40 years old. In classic cases, common treatment options include nonsteroidal anti-inflammatory drugs (NSAIDS) like indomethacin (orally or topically) or acemetacin, as well as topical and systemic steroids, isotretinoin (retinoid), itraconazole (antifungal), permethrin (insecticide), and antibiotics like dapsone. Unfortunately, classic EPF usually continues for years with recurrent relapses and remissions. Some patients are able to achieve long-lasting remissions with indomethacin alone or in combination with dapsone.
  • HIV-associated EPF occurs in patients with advanced HIV. This type of EPF may develop at any age and it is considered the most common form. Nearly 10% of HIV patients develop EPF, according to one survey. HIV patients who develop EPF should begin highly active antiretroviral therapy (HAART) if they are not already receiving treatment. HAART will help reconstitute (restore) the immune system of HIV patients. Other treatments are available, but symptoms usually recur once treatment is discontinued.
  • Infantile EPF occurs in infants and children. Most individuals who have the infantile form of the disease develop the condition within the first year of life. However, some babies are born with the condition. The infantile type of EPF responds well to topical corticosteroids like hydrocortisone. Eosinophilic pustulosis of the scalp in infancy/childhood is a recurrent skin condition that can be relieved by topical corticosteroids.
  • According to the National Institutes of Health (NIH), EPF is a rare disease. The most common variant is HIV-associated EPV. However, the exact incidence of the disease is unknown.
  • Men are five times more likely to develop EPF than women. However, since the cause remains unknown, more research is necessary to determine the reason behind this.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. DermNet NZ. . Accessed May 13, 2009.
  2. Lazarov A, Wolach B, Cordoba M, et al. Eosinophilic pustular folliculitis (Ofuji disease) in a child. Cutis. 1996 Aug;58(2):135-8. .
  3. Lucky AW, Esterly NB, Heskel N, et al. Eosinophilic pustular folliculitis in infancy. Pediatr Dermatol. 1984 Jan;1(3):202-6. .
  4. Natural Standard: The Authority on Integrative Medicine. . Copyright © 2009. Accessed May 13, 2009.
  5. Skin Disorders Guide. . Accessed May 13, 2009.

Causes
  • The causes of all three types of EPF remain unknown. Some researchers suggest that the condition is caused by an allergic reaction to dermatophytes (parasitic fungi that cause skin infections) or saprophytic fungi (fungi that live on decaying or decomposing organic matter), such as Pityrosporum ovale.This theory is supported by the positive therapeutic response of some patients to oral therapy with itraconazole (antifungal drug). Also, bacteria similar to Leptotrichia buccalis were found in one biopsy specimen of a patient with HIV-associated EPF. The disease responded to oral metronidazole (antibiotic used to treat bacterial infections).
  • Some researchers speculate that overgrowth of Malassezia or Demodex (the hair follicle mite) might be involved in the development of EPF.
  • Another theory is that HIV-associated EPF is an autoimmune disorder that causes eosinophils (type of white blood cells that help fight against disease and infection) to mistakenly attack the sebum (oils produced in the skin).

Symptoms
  • The symptoms for all three variants of the disease are generally the same. About 20% of patients suffer from reddish bumps and/or pimples on the hands or feet, which may be the first signs of the disease.
  • Patients experience dandruff or dry, scaly skin on the head and trunk of the body. Papulopustules (white-headed pimples that are filled with pus) usually appear around hair follicles on the face and trunk, although the extremities (arms and legs) may also be involved. The classic form tends to affect the palms and soles of the feet. In children, the scalp is more frequently involved. Individual papulopustules may be larger in the classic form (up to 20 to 50mm in diameter) than the HIV-associated or infantile form, which are typically about one to three millimeters in diameter.
  • The infection may itch or be tender. However, the classic variant of the disease is typically less itchy than the other two forms.
  • Uncommon symptoms, including nonfolilcular papules (small lesions on the skin that are not near hair follicles) and hives are often seen in infants and HIV patients.

Diagnosis
  • Skin biopsy: A skin biopsy is the standard diagnostic test for eosinophilic pustular folliculitis (EPF). During the procedure, a local anesthetic may be applied to numb the skin that will be sampled. The healthcare provider will then use a scalpel to either cut out or shave off a small sample of skin. The sample is then analyzed under a microscope. Skin biopsies reveal lymphocytic and eosinophilic inflammation around the hair follicles.
  • Complete blood count: During a complete blood count, a small sample of blood is taken from the patient and analyzed under a microscope in a laboratory. A complete blood count is not considered a diagnostic test for EPF. However, a blood test may detect an increased number of eosinophils in the blood, which may indicate EPF. Eosinophils make up about one to three percent of a healthy person's white blood cells, which is about 350 to 650 eosinophils per microliter of blood.

Treatment
  • General: Because the origin and the development of eosinophilic pustular folliculitis (EPF) are not fully understood, there is currently no established treatment regimen, and scientific studies have not been performed to determine the most effective treatment for this condition. Treatment generally focuses on decreasing the inflammation and itching.
  • In classic cases, common treatment options include nonsteroidal anti-inflammatory drugs (NSAIDS) like indomethacin (orally or topically) or acemetacin, as well as topical and systemic steroids, isotretinoin (retinoid), itraconazole (antifungal), permethrin (insecticide), and antibiotics like dapsone. Unfortunately, classic EPF usually continues for years with recurrent relapses and remissions. Some patients are able to achieve long-lasting remissions with indomethacin alone or in combination with dapsone.
  • HIV patients should begin highly active antiretroviral therapy (HAART) if they are not already receiving treatment. HAART will help reconstitute (restore) the immune system of HIV patients. Other treatments are available, but symptoms usually recur once treatment is discontinued. Additional treatment options may include oral itraconazole along with an oral sedating antihistamine before sleep if pruritis (itching) is severe, oral metronidazole, and ultraviolet therapy.
  • The infantile variant of EPF responds well to topical corticosteroids like hydrocortisone.
  • Antibiotics: Antibiotics like dapsone (Avlosulfon®) may help improve symptoms of the disease, especially in the classic form. These drugs are used to treat bacterial infections, which may cause the disease.
  • Antihistamines: Antihistamines like cyproheptadine (Periactin®) and cetirizine (Zyrtec®) may help relieve itching and inflammation associated with EPF. These medications are often taken before bed in HIV patients who are suffering from pruritic (itchy) EPF.
  • Corticosteroids: Corticosteroids like prednisone (Deltasone®, Orasone®, or Liquid Pred®) have been used to decrease inflammation associated with all types of EPF. Prednisone may slow growth and development in children, and therefore should only be used under the strict supervision of a qualified healthcare provider. The infantile type of EPF responds well to topical corticosteroids like hydrocortisone.
  • Highly active antiretroviral therapy (HAART): In patients with HIV-associated disease, antiretroviral therapy tends to greatly diminish or even eliminate the symptoms of this disorder. Highly active antiretroviral therapy (HAART) is a combination of antiretroviral drugs that help reconstitute (restore) the immune system of HIV patients. This strategy, developed by the National Institute of Allergy and Infectious Diseases (NIAID)-support researchers, usually combines drugs from at least two different classes of antiretroviral drugs. While these drugs cannot cure HIV infection or AIDS, they can suppress the virus.
  • Currently, the U.S. Food and Drug Administration (FDA) has approved 28 antiretroviral drugs to treat HIV. These drugs fall into three major classes: reverse transcriptase (RT) inhibitors, fusion inhibitors, and protease inhibitors. In July 2006, the FDA approved a multi-class combination called Atripla®.
  • Reverse transcriptase (RT) inhibitors disrupt the reverse transcription stage in the HIV lifecycle. During this stage, an HIV enzyme, known as reverse transcriptase, converts HIV RNA to HIV DNA. There are two main types of RT inhibitors - non-nucleoside RT inhibitors and nucleoside/nucleotide RT inhibitors.
  • Non-nucleosideRT inhibitors bind to reverse transcriptase, preventing HIV from converting the HIV RNA into HIV DNA. Approved non-nucleoside RT inhibitors include Rescriptor®, Sustiva®, and Viramune®.
  • Nucleoside/nucleotide RT inhibitors serve as faulty DNA building blocks. Once they are incorporated into the HIV DNA, the DNA chain cannot be completed. Therefore, the drugs prevent HIV from replicating inside a cell. Approved drugs include Combivir®, Emtriva®, Epivir®, Epzicom®, Hivid®, Retrovir®, Trizivir®, Truvada®, Videx EC®, Videx®, Viread®, Zerit®, and Ziagen®.
  • Fusion inhibitors prevent the virus from fusing with the cellular membrane, thus blocking entry into the cell. Only one fusion inhibitor, Fuzeon®, is FDA-approved.
  • Protease inhibitors (PIs) interfere with the protease enzyme that HIV uses to produce infectious viral particles. PIs prevent viral replication by inhibiting the activity of protease, an enzyme used by the virus to cleave nascent proteins for final assembly of new virons. FDA-approved protease inhibitors include Agenerase®, Aptivus®, Crixivan®, Invirase®, Kaletra®, Lexiva®, Norvir®, Prezista®, Reyataz®, and Viracept®.
  • Itraconazole (Sporanox®): Patients suffering from HIV-associated EPF are usually given itraconazole (Sporanox®) capsules, which treat fungal infections that may cause EPF. Itraconazole capsules are usually taken twice daily for one week, followed by three weeks of no treatment. The patient then receives the medication twice daily for an additional week.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs): Nonsteroidal anti-inflammatory drugs (NSAIDs) like indomethacin (Indocin® or Indochron ER®) have been used to reduce inflammation associated with EPF. According to Japanese dermatologists (skin doctors), indomethacin (oral or topical) is by far the most effective treatment for the classic form of EPF. However, the mode of its action in this disease is still poorly understood.
  • Oral metronidazole: Some patients with HIV-associated EPF may respond to oral metronidazole (like Flagyl®). Metronidazole eliminates bacteria and other microorganisms that cause infections of the skin, as well as the reproductive system, gastrointestinal tract, skin, vagina, and other areas of the body. It is usually taken two or three times a day for five to ten days or longer.
  • Permethrin: Permethrin is a topical (applied to the skin) cream that has been used to kill parasites, which may cause EPF. This treatment is most commonly used in patients suffering from the classic variant of EPF. While this treatment has shown to be effective, lesions reappear with discontinuation of treatment.
  • Retinoids: Retinoids like isotretinoin (Accutane®) have been used to treat papulopustules (white-headed pimples that are filled with pus) caused by EPF. Retinoids should not be taken during pregnancy because of the risk of birth defects. Isotretinoin is taken by mouth, usually twice a day with meals.
  • Ultraviolet therapy: Ultraviolet therapy has also been used to treat EPF. Treatment with ultraviolet B or with ultraviolet A and a photosensitizing chemical called psoralen may be beneficial in HIV patients . However, skin lesions typically recur once the phototherapy id discontinued.

Integrative therapies
  • Note: Currently, there is insufficient evidence available on the safety and effectiveness of integrative therapies for the treatment of eosinophilic pustular folliculitis (EPF). The integrative therapies listed below should be used only under the supervision of a qualified healthcare provider, and should not be used in replacement of other proven therapies or preventive measures.
  • Strong scientific evidence:
  • Vitamin A: Derivatives of vitamin A, retinoids, are used to treat skin disorders such as acne. Vitamin A supplements should not be used simultaneously with prescription medications, especially Accutane®, due to a risk of increased toxicity.
  • Avoid if allergic or hypersensitive to vitamin A. Vitamin A toxicity can occur if taken at high dosages. Use cautiously with liver disease or alcoholism. Smokers who consume alcohol and beta-carotene may be at an increased risk for lung cancer or heart disease. Vitamin A appears to be safe in pregnant women if taken at recommended doses; however, vitamin A excess, as well as deficiency, has been associated with birth defects. Excessive doses of vitamin A have been associated with central nervous system malformations. Use cautiously if breastfeeding because the benefits or dangers to nursing infants are not clearly established.
  • Good scientific evidence:
  • Zinc: Several studies identify a positive correlation between serum zinc levels and severity of acne, however others did not, and it remains to be determined to which degree internal zinc levels may correlate with the severity of acne. Based on high quality studies, topical or oral use of zinc seems to be a safe and effective treatment for acne vulgaris.
  • Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride since studies have not been done on its safety or effectiveness. Avoid with kidney disease. Use cautiously if pregnant or breastfeeding.
  • Unclear or conflicting scientific evidence:
  • Calendula: Limited early research suggests that calendula extracts may reduce skin inflammation. Human studies are lacking in this area.
  • Avoid if allergic to plants in the Aster/Compositae family such as ragweed, chrysanthemums, marigolds, and daisies. Use cautiously in patients taking sedatives, blood pressure medications, cholesterol medications, blood sugar-altering agents, and immunomodulators. Use cautiously with diabetes and in children. Avoid if pregnant or breastfeeding.
  • Chamomile: Chamomile has been used medicinally for thousands of years, and is widely used in Europe. It is a popular treatment for numerous ailments, including skin infections and skin inflammation. The German Commission E has approved the internal and the external use of chamomile (Matricaria recutita L.) for inflammatory and bacterial skin diseases. However, little research has been done on topical chamomile for skin conditions. Further clinical research is necessary before a recommendation can be made.
  • Avoid if allergic to chamomile or any related plants such as aster, chrysanthemum, mugwort, ragweed, or ragwort. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Use cautiously if driving or operating machinery. Avoid if pregnant or breastfeeding.
  • Guggul: Guggul (Commiphora mukul), an herbal supplement commonly used in India, has been found to possess anti-inflammatory properties and has been suggested as an oral therapy for acne. Preliminary data from small, methodologically weak human studies suggest possible short-term improvements in the number of acne lesions.
  • Caution is advised when taking guggul supplements as adverse effects including drug interactions are possible. Guggul is not recommended during pregnancy or breastfeeding unless otherwise advised by a doctor. Avoid if allergic to guggul. Avoid with a history of thyroid disorders, anorexia, bulimia or bleeding disorders. Signs of allergy to guggul may include itching and shortness of breath. Avoid if pregnant or breastfeeding.
  • Marshmallow: Marshmallow extracts have traditionally been used to treat inflammatory skin conditions. Several laboratory experiments, mostly in the 1960s, reported marshmallow to have anti-inflammatory activity but limited human study is available. Safety, dosing, and effectiveness compared to other anti-inflammatory agents have not been examined.
  • Historically, marshmallow is generally regarded as being safe in healthy individuals. However, since studies have not evaluated the safety of marshmallow, proper doses and duration in humans are not known. Allergic reactions may occur. There is not enough scientific evidence to support the safe use of marshmallow during pregnancy or breastfeeding.
  • Para-aminobenzoic acid: Para-aminomethylbenzoic acid (PABA) may be useful in the treatment of lichen slerosus, a benign, progressive dermatologic condition characterized by inflammation, pruritus (itching), and pain, especially in the anogenital region (involving the anus and genitals). Additional investigations are needed regarding the use of PABA for inflammatory skin disorders.
  • Avoid with known hypersensitivity to PABA or its derivatives. Discontinue use if rash, nausea, or anorexia occurs. Avoid oral use in children and pregnant or nursing women. Use cautiously in patients with renal or liver disease. PABA should not be given concurrently with sulfonamides. Use cautiously in patients with bleeding disorders or taking anticoagulants. Use cautiously in patients with diabetes or hypoglycemia.
  • Tea tree oil: Topical application of tea tree (Melaleuca alternifolia) oil may be beneficial in acne vulgaris. The tea tree is found in Australia and its oil is used for antibacterial effects, including positive studies on preventing and healing acne outbreaks. Tea tree oil is applied (diluted) onto areas with acne, three times daily.
  • Avoid allergic or hypersensitive to tea tree oil (Melaleuca alternifolia), any of its constituents, balsam of Peru, benzoin, colophony (rosin) tinctures, eucalyptol, or other members of the Myrtle (Myrtaceae) family. Avoid taking tea tree oil by mouth. Avoid if taking antineoplastic agents. Use tea tree oil applied to the skin cautiously in patients with previous tea tree oil use. Avoid if pregnant or breastfeeding.
  • Thyme: Historically, thyme has been used topically for a number of inflammatory skin disorders. Results are mixed. Additional study is needed in this area.
  • Avoid with known allergy/hypersensitivity to members of the Lamiaceae (mint) family or to any component of thyme, or to rosemary (Rosmarinus officinalis). Avoid oral ingestion or non-diluted topical application of thyme oil due to potential toxicity. Avoid topical preparations in areas of skin breakdown or injury, or in atopic patients, due to multiple reports of contact dermatitis. Use cautiously in patients with gastrointestinal irritation or peptic ulcer disease due to anecdotal reports of gastrointestinal irritation. Use cautiously in patients with thyroid disorders due to observed anti-thyrotropic effects in animal research of the related species Thymus serpyllum. Avoid if pregnant or breastfeeding.
  • Witch hazel: Although witch hazel has been commonly used to relieve minor skin irritation, there are few human studies evaluating its use for this purpose. High-quality human study is needed for a conclusion to be made.
  • Avoid if allergic or sensitive to witch hazel. Avoid if pregnant or breastfeeding. Use cautiously in people with liver or kidney disorders, diabetes, and in children.

Prevention
  • Currently, there is no known method of prevention for eosinophilic pustular folliculitis (EPF).

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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