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Dermatology > DISEASES OF THE ADNEXA
Eosinophilic Pustular Folliculitis
Article Last Updated: Feb 21, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Marian Dmochowski, MD, Assistant Professor, Department of Dermatology, University School of Medicine at Poznan, Poland
Marian Dmochowski is a member of the following medical societies: Society for Investigative Dermatology
Coauthor(s):
Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Editors: Takeji Nishikawa, MD, Emeritus Professor, Department of Dermatology, Keio University School of Medicine; Director, Samoncho Dermatology Clinic; Managing Director, The Waksman Foundation of Japan Inc; Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center; Jeffrey Meffert, MD, Assistant Clinical Professor of Dermatology, University of Texas Health Science Center-San Antonio; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Author and Editor Disclosure
Synonyms and related keywords:
EPF, Ofuji's disease, Ofuji disease, eosinophilic folliculitis, HIV-associated eosinophilic folliculitis, HIV-related eosinophilic folliculitis, infantile/childhood eosinophilic pustular folliculitis, sterile eosinophilic pustulosis, eosinophilic pustular dermatosis, infantile/childhood eosinophilic pustulosis of the scalp
Background
In 1965, Ise and Ofuji described a 42-year-old Japanese housewife with a possible follicular variant of subcorneal pustular dermatosis. The patient had crops of follicular pustules on her back, face, chest, and upper arms representing histologic subcorneal pustulosis of the upper hair follicles. The patient also had a leukocytosis of 14,100 white cells/µL, 8% of which were eosinophils. In 1970, Ofuji et al described 3 additional patients and proposed that this new entity be called eosinophilic pustular folliculitis (EPF). The use of the term folliculitis has been challenged for this disorder because hair follicles are not seen on the palms or the soles, which may be affected.
Three variants of this disorder have been described: classic EPF (as originally described by Ofuji), HIV-associated EPF, and infantile EPF. Some investigators prefer to consider these 3 distinct disorders. Of the 3, the infantile variety is by far the least characterized. Because the exact nature of these conditions is unknown, whether these conditions are 3 interrelated forms of a single disease or 3 distinct dermatoses is unclear. These conditions share a common pathologic feature, namely a noninfectious eosinophilic infiltration of the hair follicles.
Pathophysiology
A histologic resemblance exists between EPF and fungal folliculitis. Some investigators have speculated that EPF is due to hyperreactivity to dermatophytes or saprophytic fungi, such as Pityrosporum ovale, in association with a disordered immune system. This concept is supported by the favorable therapeutic response of some patients to oral itraconazole therapy. The follicle mite, Demodex, has also been considered a possible triggering agent. In certain patients, a combination of Pityrosporum species and Demodex species might play a role in the pathogenesis of the disease. An aberrant helper T-cell type 2 immune response to a follicular antigen, such as Demodex, might be involved in the pathogenesis of HIV-associated EPF (see Media File 3). An anaerobic organism similar in morphology to Leptotrichia buccalis has been found in one biopsy specimen of a patient with HIV-associated Ofuji disease; the disease responded to oral metronidazole. Others believe that at least the HIV-associated form is an autoimmune disorder with the sebaceous gland cell or a constituent of sebum serving as an autoantigen. A single case has been reported of a patient with Ofuji disease with pemphiguslike antibody detected by direct immunofluorescence on both lesional skin and healthy skin and by indirect immunofluorescence on human skin but not on guinea pig esophagus. Yet another patient with Ofuji disease and high titers of circulating immunoglobulin G and immunoglobulin M antibodies to the cytoplasm of the basal cells of the epidermis and the outer sheath of hair follicles has also been described. Another theory is that eosinophilic chemotactic factors from skin surface lipids may be involved. A selective migration of leukocyte factor antigen-1–positive eosinophils and lymphocytes to hair follicles may be explained by intercellular adhesion molecule-1 expression by keratinocytes on follicular epithelium but not on epidermis. The expression of endothelial-leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1 by vascular endothelium around hair follicles may also explain this migration. Eosinophils infiltrating into the dermis and the follicular epidermis express neuronal nitric oxide synthase. Activated eosinophils release major basic protein with subsequent tissue damage. In addition to degranulating eosinophils, degranulating mast cells are present in the skin of most patients with HIV-associated eosinophilic folliculitis, which suggests a role for both of these cell types in the pathogenesis of this disease.
Frequency
International
This is an uncommon disorder, except in the AIDS population. The peak incidence of the classic disease is in the second to fourth decades. The peak incidence is usually in the first year of life for the infantile form; EPF may be congenital in infantile cases. It may be seen at any age with HIV disease, with an incidence of almost 10% in one survey. EPF is most frequent in association with a low CD4 count.
Mortality/Morbidity
The main morbidity is chronic persistent pruritus, which, especially in the HIV-related form, can interfere with activities of daily living.
Race
All races are affected. The classic form described by Ofuji mainly occurs in Japanese people in Japan. HIV infection is the most common medical condition associated with EPF, at least in whites.
Sex
EPF is more common in men than in women.
- In the classic form, the ratio of men to women is about 5:1.
- With HIV disease, an overwhelming male prevalence exists.
- Even in infants, the disease occurs more often in boys than in girls.
History
- The distribution tends to be a seborrheic one on the head and the trunk. About a fifth of patients have palmar and/or plantar plaques, which may be the first sign appearing weeks or months before other clinical features.
- Lesions are less commonly pruritic with the classic type than in the other 2 forms.
Physical
Patients with EPF in the classic form have chronically recurrent crops of sterile follicular papulopustules with peripheral extension and central clearing.
- Papulopustules with or without plaques tend to favor the face and the trunk, although the extremities may also be involved. With the classic form, the palms and the soles may also be affected. In children, the scalp, particularly at the vertex, is most frequently involved.
- Some patients may have features of coexistent Ofuji disease and eosinophilic lymphoid granuloma (Kimura disease).
- Individual papulopustules may be larger in the classic form, up to 20-50 mm in diameter, rather than the 1-3 mm in diameter seen in patients with HIV disease and in infants; peripheral extension with central clearing may be much less frequent in these 2 forms than in the classic one, which often has an erythematous base. The latter tends to heal more commonly with postinflammatory hyperpigmentation.
- No systemic involvement is evident, although a peripheral leukocytosis and eosinophilia may be seen. Atypical features, such as nonfollicular papules and urticarial plaques, are often evident in patients with HIV disease and in infants.
Causes
The cause of EPF is unknown. Possible etiologies are discussed in Pathophysiology. Reports have described Asian patients in whom EPF seemed to be associated with silicone tissue augmentation or autologous peripheral blood stem cell transplantation. A middle-aged Japanese woman has been described in whom EPF was induced by a combination of allopurinol and timepidium bromide as suggested by the results of an oral provocation test with both drugs.
Acneiform Eruptions
Acropustulosis of Infancy
Atopic Dermatitis
Dermatitis Herpetiformis
Erythema Multiforme
Erythema Toxicum Neonatorum
Folliculitis
Impetigo
Langerhans Cell Histiocytosis
Papular Urticaria
Pemphigus Foliaceus
Pemphigus Herpetiformis
Pemphigus Vulgaris
Perifolliculitis Capitis Abscedens Et Suffodiens
Psoriasis, Pustular
Scabies
Seborrheic Dermatitis
Subcorneal Pustular Dermatosis
Tinea Corporis
Transient Neonatal Pustular Melanosis
Other Problems to be Considered
Candidosis
Other types of folliculitis
Demodex folliculitis (demodicosis)
Impetigo herpetiformis
Acrodermatitis continua
Folliculitis decalvans
Follicular mucinosis
Erosive pustular dermatosis of the scalp
Pustular drug eruptions
Pemphigus foliaceus and pemphigus vulgaris initially presenting as pemphigus herpetiformis
Lab Studies
- Cytologic smears show abundant eosinophils.
- In the classic form, mild-to-moderate leukocytosis and eosinophilia are often evident. The latter is seen in about one half of patients.
- With HIV disease, the CD4 count is often less than 300 cells/µL.
- Infants with this disorder may have an elevated serum immunoglobulin E level with reduced serum immunoglobulin G and immunoglobulin A levels and diminished neutrophil chemotactic activity.
- Because childhood EPF may be associated with AIDS, lymphoma, leukemia, and other hematologic diseases, a thorough systemic evaluation is indicated.
- Take skin swabs for microscopy and culture and scrapings for mycologic analysis when a microbial infection or superinfection is suspected.
- Consider HIV- and non–HIV-related causes of immunodeficiency.
- When vesicles predominate, perilesional skin may be examined with direct immunofluorescence, and serum may be evaluated with indirect immunofluorescence on healthy human skin and/or desmoglein 1/desmoglein 3 enzyme-linked immunosorbent assay to exclude pemphigus foliaceus or pemphigus vulgaris. Both of these conditions might initially be evident as pemphigus herpetiformis, thus looking like EPF both clinically and histopathologically.
Histologic Findings
Examine fresh, unexcoriated papulovesicles histologically, ideally in serial sections. Transverse sectioning may be needed if routine vertical sections give equivocal results. Use routine hematoxylin and eosin stain as well as special stains for fungi and bacteria. Subcorneal pustules of predominately eosinophils may be evident in the epidermis and the outer root sheath of hair follicles. Hair and sebaceous gland structures may be infiltrated with eosinophils, plus a few neutrophils and mononuclear cells (see Media File 5). A patchy sebaceous lysis is observed in certain cases of HIV-related EPF. Follicular eosinophilic abscesses are infrequently observed in HIV-associated cases of Ofuji disease. Infantile EPF of the scalp may show an interfollicular dermal infiltrate with a substantial admixture of eosinophils and flame figures but not follicular spongiosis or degeneration. Sometimes, mucin deposition can be observed in the hair follicles. Histopathologic study may reveal the coexistence of Ofuji disease and follicular mucinosis in patients with or without concomitant HIV infection. The lymphocytes in the HIV-associated type are predominately CD8+ lymphocytes. Palmar and plantar plaques show subcorneal or intraepidermal eosinophilic abscesses and spongiosis. Small foci of acantholysis may be seen in individual cases of EPF.
Medical Care
A variety of options have been described with variable results.
- In classic cases, common options for treatment include indomethacin (orally or topically) and its newer derivative acemetacin, dapsone, topical and systemic steroids, isotretinoin, itraconazole, permethrin, interferon, and antibiotics. The experience of Japanese dermatologists is that indomethacin is by far the most effective in the classic form, although the mode of its action in this disease is still poorly understood.
- Ultraviolet therapy with ultraviolet B or with ultraviolet A and psoralen plus ultraviolet A may be beneficial. The authors tend to try topical itraconazole cream first in patients with HIV-associated disease, adding an oral sedating antihistamine for bedtime use if pruritus is severe. Cetirizine seems to be a favorite because of its preferential effect on eosinophils, although these authors often prefer 4 mg of cyproheptadine at bedtime.
- In patients with HIV-associated disease, antiretroviral therapy tends to greatly diminish or even eliminate the severity of this disorder.
- Some patients with HIV-associated Ofuji disease may respond to oral metronidazole.
Because the etiology and the pathogenesis of EPF have not been fully elucidated, no established treatment schemes exist. A number of options have been tried with various results; however, no controlled treatment trials have been performed for this condition. Oral indomethacin consistently appears to be most beneficial, at least in the classic form of the disease, whereas permethrin and cyproheptadine might alleviate the symptoms in some patients, especially in HIV-associated cases of the disease. The correction of immunodeficiency in HIV-related EPF may clear the skin lesions. Systemic treatment modalities may not be needed for an infantile/childhood variant of EPF because most cases respond to topical corticosteroids.
An alternative therapeutic option in patients with a long-term history of unsuccessful response to conservative therapy is ionizing radiation (Wilson, 2002). In recent years, reports have suggested that EPF may respond to treatment with topical tacrolimus or transdermal nicotine patches. Additionally, one case report suggests that treatment with interferon gamma intravenously followed by oral ciclosporin may yield longer-lasting benefit by correcting an aberrant T helper cell 2 type immune response implicated in the pathogenesis of this dermatosis (Sugita, 2006).
Drug Category: Nonsteroidal anti-inflammatory drugs
These agents inhibit inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.
| Drug Name | Indomethacin (Indocin) |
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| Description | A potent inhibitor of cyclooxygenase, which may decrease the local production of arachidonic acid derived chemotactic factors for eosinophils present in sebum (eg, 12-L-hydroxy-5,8,10-heptadecatrienoic acid and/or prostaglandin). |
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| Adult Dose | 50 mg PO pc tid; taper as symptoms resolve |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; GI bleeding or renal insufficiency; treatment of peri-operative pain in setting of coronary artery bypass graft; neonates with active bleeding, infection, necrotizing enterocolitis, severe renal failure, thrombocytopenia, or coagulation defects; patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs |
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| Interactions | Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, ACE inhibitors, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate and lithium toxicity; phenytoin levels may be increased when administered concurrently; concurrent administration with clopidogrel should be monitored closely for bleeding; coadministration with quinolones may increase risk of seizures |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks.
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| Precautions | Category D in third trimester of pregnancy (may cause closure of ductus arteriosus); acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; reversible leukopenia may occur (discontinue if leukopenia, granulocytopenia, or thrombocytopenia persists)
Adverse effects include anemia, aplastic anemia, asthma , bronchospasm, blurred vision including corneal deposit and retinal disorder, inflammatory disorder of digestive tract including gastrointestinal perforation and ulcer, cardiac dysrhythmia, chest pain and myocardial infarction, congestive heart failure, cerebrovascular accident, epilepsy, hearing loss, hematuria, nephrotic syndrome, newborn renal dysfunction, dyspnea, edema, hypertension, and transitory neonatal hyperkalemia |
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Drug Category: Scabicides
These agents might be useful in some HIV-associated cases of EPF in which the commensal hair follicle mite, Demodex, might be a triggering antigen; however, lesions reappear with discontinuation of treatment.
| Drug Name | Permethrin (Elimite) |
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| Description | Acts on the nerve cell membrane to disrupt sodium channel current by which the polarization of the membrane is regulated. Delayed repolarization and paralysis of pests are the result. |
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| Adult Dose | Initial: Massage 5% cream or 1% liquid into affected skin qd
Maintenance: 1-2 applications/wk |
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| Pediatric Dose | <2 years: Not established
>2 years: Apply as in adults |
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| Contraindications | Documented hypersensitivity |
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| Interactions | None reported |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks.
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| Precautions | May exacerbate pruritus, erythema, and edema temporarily; use in pregnancy only if clearly needed |
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Drug Category: Antihistamines
These agents may alleviate itching in some HIV-associated cases of EPF. Sedating forms may be more effective (especially for nocturnal pruritus).
| Drug Name | Cyproheptadine (Periactin) |
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| Description | For the symptomatic relief of allergic symptoms caused by histamine released in response to allergens and skin manifestations. |
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| Adult Dose | 4 mg PO hs; not to exceed 0.5 mg/kg/d |
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| Pediatric Dose | <2 years: Not established
2-6 years: 2 mg PO hs; not to exceed 12 mg/d
>6-14 years: 4 mg PO bid/tid; 16 mg/d maximum
>14 years: Administer as in adults |
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| Contraindications | Documented hypersensitivity; newborn or premature infants; breastfeeding; during MAOI therapy; in cases of angle-closure glaucoma; stenosing peptic ulcer; symptomatic prostatic hypertrophy; bladder neck obstruction; pyloroduodenal obstruction; elderly and/or debilitated patients |
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| Interactions | MAOIs prolong and intensify the anticholinergic effects; may have additive effects with alcohol and other CNS depressants; as a serotonin antagonist, may oppose effects of agents that inhibit serotonin reuptake; may blunt thyrotropin response |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks.
|
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| Precautions | May diminish mental alertness; has an atropinelike action; caution in patients with a predisposition to urinary retention, history of bronchial asthma, increased intraocular pressure, hyperthyroidism, cardiovascular disease, or hypertension; may thicken bronchial secretions caused by anticholinergic properties, and may inhibit expectoration and sinus drainage |
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| Drug Name | Hydroxyzine (Atarax) |
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| Description | Antagonizes H1 receptors in periphery. May suppress histamine activity in subcortical region of CNS. |
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| Adult Dose | 25-100 mg PO qd/qid |
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| Pediatric Dose | 0.6 mg/kg/dose PO q6h |
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| Contraindications | Documented hypersensitivity; early pregnancy |
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| Interactions | CNS depression may increase with alcohol or other CNS depressants |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
|
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| Precautions | Associated with clinical exacerbations of porphyria (may not be safe for patients with porphyria); ECG abnormalities (alterations in T waves) may occur; may cause drowsiness |
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Prognosis
- Unfortunately, the classic/Japanese form of this condition usually continues for years with recurrent relapses and remissions. Some patients have achieved long-lasting remissions with indomethacin alone or in combination with dapsone.
- Patients with HIV-associated disease may benefit from highly active antiretroviral therapy. Treatment that restores immunity in individuals with HIV infection may clear their skin lesions, which otherwise are chronic and persistent. In the absence of improvement of the underlying immunodeficiency, HIV-associated eosinophilic folliculitis usually does not respond to any treatment; even with ultraviolet B and psoralen plus ultraviolet A phototherapy, the skin lesions recur on discontinuation of phototherapy.
- Eosinophilic pustulosis of the scalp in infancy/childhood is a self-limited, albeit recurrent, dermatosis that can be relieved by topical corticosteroids.
Medical/Legal Pitfalls
- Failure to exclude other infectious diseases is a pitfall. A comprehensive microbial examination should be performed to exclude the possibility of an infectious disease in patients with EPF-like clinical and histopathologic features.
| Media file 1:
A patchy lesion on the cheek in a patient with eosinophilic pustular folliculitis. Courtesy of Professor T. Nishikawa, Department of Dermatology, Keio University School of Medicine, Tokyo, Japan. |
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Media type: Photo
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| Media file 2:
Widespread hyperpigmented patches on the back and the arms in a patient with eosinophilic pustular folliculitis. Courtesy of Professor T. Nishikawa, Department of Dermatology, Keio University School of Medicine, Tokyo, Japan. |
 | View Full Size Image | |
Media type: Photo
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| Media file 3:
A 51-year-old Japanese man without a concomitant HIV infection with pustular eosinophilic folliculitis. Courtesy of Professor Akimichi Morita, Nagoya City University Medical School, Nagoya, Japan. |
 | View Full Size Image | |
Media type: Photo
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| Media file 4:
Transverse section from a 21-year-old man with eosinophilic pustular folliculitis. A perifollicular inflammatory infiltrate containing numerous eosinophils is present (hematoxylin and eosin, original magnification X400). |
 | View Full Size Image | |
Media type: Photo
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| Media file 5:
Vertical section from a 3-year-old girl with eosinophilic pustular folliculitis. A perifollicular inflammatory infiltrate containing eosinophils is present (hematoxylin and eosin, original magnification X200). |
 | View Full Size Image | |
Media type: Photo
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Eosinophilic Pustular Folliculitis excerpt Article Last Updated: Feb 21, 2007
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