Eosinophilic Pustular Folliculitis

Eosinophilic pustular folliculitis (EPF), also known as Ofuji disease, is a disease that manifests with follicular papules or pustules. Its variants include a classic type that occurs most commonly in Japan, an HIV-associated type, an infantile type, a type that occurs on the palms and soles, a rare medication-associated variant, and a rare neoplasia-associated variant.A wide range of medications has been used to treat EPF. Topical corticosteroids are the first-line treatment option for EPF. Topical tacrolimus seems to be useful initial therapy as well. Oral indometacin (50-75 mg/day) is an effective treatment of classic EPF although it can induce peptic ulcers. For treatment of HIV-associated EPF when topical corticosteroids and indometacin do not work, various other treatments should be considered. These treatment options include cetirizine 20-40 mg/day, metronidazole 250 mg three times a day, itraconazole starting at a dosage of 200 mg/day and increasing to 300-400 mg/day, and topical permethrin. If these treatments do not work phototherapy with UVB is the 'gold standard' of treatment and is often curative. Treatments with less certain risk-benefit ratios but with some efficacy include PUVA (psoralen + UVA) photochemotherapy, oral corticosteroids, synthetic retinoids (i.e. isotretinoin 1 mg/kg/day), and acitretin (0.5 mg/kg/day), oral cyclosporine (ciclosporine) 5 mg/kg/day, interferon (IFN)-alpha-2b, and IFNgamma. Minocycline 100mg twice daily and dapsone 50-100mg twice daily have been used with some effect. The use of highly active antiretroviral therapy for HIV has resulted in the amelioration of EPF as CD4 cell counts rise above 250/mm(3). The diversity of clinical presentations and affected populations make it seem that EPF is a reaction pattern as much as a disease and that therapy should be tailored to the variant of EPF and the underlying etiology.     

HIV-associated eosinophilic folliculitis in an infant.

HIV-associated eosinophilic folliculitis (HIV-EF), which is a well-known entity in adults, has not been described in children. Although Ofuji's disease (OD) or eosinophilic pustular folliculitis (EPF) has been described in children and shares histopathologic features with HIV-EF, it is a distinct entity with characteristic clinical features. We report the occurrence of eosinophilic folliculitis in an 8-month-old HIV-positive patient and discuss the clinical, pathologic and possible pathogenetic aspects thereof. In addition, differences in the clinical manifestations of the present case and that of I-EPF are addressed. Because of clinicopathologic similarities between the present case and HIV-associated eosinophilic folliculitis (HIV-EF) in adults, we believe that eosinophilic folliculitis in this patient represents a cutaneous manifestation of HIV infection, rather than co-incidental occurrence of the infantile form of Ofuji's disease in an HIV-positive patient.     

Clinical and histopathological differential diagnosis of eosinophilic pustular folliculitis

Eosinophilic pustular folliculitis (EPF) is an inflammatory disease characterized by repeated pruritic follicular papules and pustules arranged in arcuate plaques, and folliculotropic infiltration of eosinophils. The diagnosis of EPF is occasionally difficult and problematic because EPF may share the clinical appearance and histological findings with other diseases. Moreover, EPF has several clinical subtypes, including the classical type, infantile type and immunosuppression‐associated type. Because the therapies of EPF are relatively specific as compared to eczematous disorders, accurate diagnosis is essential for the management of EPF. Clinical differential diagnoses include tinea, acne, rosacea, eczematous dermatitis, granuloma faciale, autoimmune annular erythema, infestations and pustular dermatosis. Histologically, cutaneous diseases with eosinophilic infiltrates can be differentially diagnosed. Follicular mucinosis, mycosis fungoides and other cutaneous T‐cell lymphomas are the most important differential diagnoses both clinically and histopathologically. It should be kept in mind particularly that the initial lesions of cutaneous T‐cell lymphoma resemble EPF.     

Eosinophilic pustular folliculitis: A published work‐based comprehensive analysis of therapeutic responsiveness

Eosinophilic pustular folliculitis (EPF) is a non‐infectious inflammatory dermatosis of unknown etiology that principally affects the hair follicles. There are three variants of EPF: (i) classic EPF; (ii) immunosuppression‐associated EPF, which is subdivided into HIV‐associated (IS/HIV) and non‐HIV‐associated (IS/non‐HIV); and (iii) infancy‐associated EPF. Oral indomethacin is efficacious, especially for classic EPF. No comprehensive information on the efficacies of other medical management regimens is currently available. In this study, we surveyed regimens for EPF that were described in articles published between 1965 and 2013. In total, there were 1171 regimens; 874, 137, 45 and 115 of which were applied to classic, IS/HIV, IS/non‐HIV and infancy‐associated EPF, respectively. Classic EPF was preferentially treated with oral indomethacin with efficacy of 84% whereas topical steroids were preferred for IS/HIV, IS/non‐HIV and infancy‐associated EPF with efficacy of 47%, 73% and 82%, respectively. Other regimens such as oral Sairei‐to (a Chinese–Japanese herbal medicine), diaminodiphenyl sulfone, cyclosporin and topical tacrolimus were effective for indomethacin‐resistant cases. Although the preclusion of direct comparison among cases was one limitation, this study provides a dataset that is applicable to the construction of therapeutic algorithms for EPF.     

Eosinophilic pustular folliculitis: A review of the Japanese published works

Eosinophilic pustular folliculitis (EPF), also known as Ofuji's disease, is an inflammatory dermatosis that was first described in Japan in 1970. More than 300 cases have been reported so far, and 113 Japanese cases have been reported in Japan since 1980. To comprehend the characteristics of Japanese EPF cases, we classified these cases into three types: classic, immunosuppression‐associated (IS‐EPF), and infancy‐associated (I‐EPF). Trends in age of onset and in distribution and characterization of eruptions differed between the types. We found 91 cases of classic EPF (mean age, 39.7 years), consisting of 66 males (73%) and 25 females (27%), in most of which eruptions primarily affected the face; 18 cases of IS‐EPF (44.2 years), consisting of 15 males (83%) and three females (17%), in which eruptions affected the face less predominantly; and four cases of I‐EPF (7.0 years), consisting of two males (50%) and two females (50%), primarily affecting the scalp. The number of IS‐EPF cases has increased since the late 1990s, reflecting the increasing number of HIV‐positive patients in Japan. Systemic non‐steroidal anti‐inflammatory drugs were effective in more than 70% of cases. Dimethyl diphenyl sulfone, antibiotics including minocycline, psoralen plus ultraviolet A therapy and ultraviolet B treatments worked in some cases. Topical steroids and tacrolimus were also effective in some cases of EPF, while topical indomethacin was less effective.     

Eosinophilic pustular folliculitis: case report and review of the literature

Eosinophilic pustular folliculitis (EPF) is a rare dermatosis characterized by recurrent outbreaks of papulopustular skin lesions mainly distributed in seborrheic areas. These eruptions often are associated with peripheral blood eosinophilia and occur mainly on the face, upper back, and upper extremities. There are 3 variants: classic EPF (Ofuji disease), immunosuppression-associated EPF, and infancy-associated EPF. We report a human immunodeficiency virus (HIV)-seronegative patient with classic EPF who responded to treatment with indomethacin.     

Eosinophilic pustular folliculitis (Ofuji's disease) and non-Hodgkin lymphoma.

The authors report the third case of eosinophilic pustular folliculitis (EPF) associated with a non-Hodgkin lymphoma. The dermatosis occurred after an autologous bone marrow transplantation performed as treatment for the lymphoproliferative disorder. Although EPF was initially described as an idiopathic disease, the association of some cases with immunologic alterations or diseases, such as immunodeficiencies, suggests a possible immunopathologic event in the pathogenesis of EPF.     

Ofuji's disease: description of a case

Eosinophilic pustular folliculitis (EPF) is a rare, chronic disease of unknown cause, characterized by itchy papules or pustules and an infiltration of eosinophiles in the biopsy. EPF occurs rarely outside Japan and very few cases have been described in non-Japanese race people. The causes of the disease and its definitive treatment have not yet been established. In our patient, the presence of subcorneal pustules in the biopsies initially favored a diagnosis of pustulosis and several biopsies were necessary before a diagnosis of EPF was reached. A new case of EPF recently presented at our clinic and we have carried out an extensive revision of the disease.     

Long noncoding RNA polymorphisms influence susceptibility to endemic pemphigus foliaceus

Pemphigus foliaceus (PF) is a disease that causes painful blisters in the skin. Due to genetic and environmental reasons, the person's own immune system produces antibodies that attack proteins present in the top layer of the skin (the epidermis). Although PF is rare worldwide, there are some geographic regions where many people develop this disease, known as the endemic form of PF (EPF). In Brazil, EPF is also known as fogo selvagem. This study aimed at finding out if single changes in the DNA (called SNPs – single nucleotide polymorphisms) located in genes called lncRNA genes predispose people to EPF. There are several different variants of SNPs. The frequencies of 2,080 SNPs were compared between 229 EPF patients and 6,681 people without pemphigus (the controls). A variant of the SNP called rs7144332 was significantly more frequent among EPF patients than people without EPF, and is therefore associated with increased risk. Results for another five SNPs suggested that they also influence the susceptibility to (risk of) EPF. Further study showed that five of these six SNPs could affect the amount of lncRNAs or proteins produced by nearby genes. Along with other findings, this study shows that genetic variants of lncRNAs might contribute to the development of pemphigus, highlighting their importance in autoimmune and possibly other complex diseases.     

Transdermal nicotine patches for eosinophilic pustular folliculitis

We previously reported the clinical effectiveness of transdermal nicotine patches for the treatment of skin disorders with eosinophilic infiltration such as Kimura's disease, erythema nodosum and eosinophilic pustular folliculitis (EPF). We assessed the efficacy and safety of transdermal nicotine patches for EPF. We treated eight patients with EPF with transdermal nicotine patches and evaluated the treatment response by performing overall lesional assessment. Excellent 77and good responses were obtained in five and one patient(s), respectively. In the other two patients, the lesions remained unchanged. No severe adverse effects were observed. Our results suggest that transdermal nicotine patches may be useful and safe in the treatment of EPF.     

A Case of Eosinophilic Pustular Folliculitis (Ofuji's Disease) Induced by Patch and Challenge Tests with Indeloxazine Hydrochloride

A 73-year-old male developed disseminated erythema over his entire body after exposure to indeloxazine hydrochloride, a cerebral activator. Patch testing with indeloxazine hydrochloride showed a positive reaction, and plaques, vesicles and pustules developed on the face after the patch test. These had the pathologic feature of eosinophilic pustular folliculitis (EPF, Ofuji's disease). A challenge test also provoked eruptions on the face, trunk, arms and legs, which were compatible with EPF. Moreover, both the patch and challenge tests with indeloxazine hydrochloride induced eosinophilia. This is the first report of drug allergy-induced EPF, where drug sensitivity induced an abnormal eosinophilic response mimicking EPF.     

Eosinophilic pustular folliculitis (Ofuji's disease) in a patient with silicone tissue augmentation

Eosinophilic pustular folliculitis (EPF) (Ofuji's disease) is a rare dermatosis of unknown etiology. We describe a 45-year-old Chinese woman who developed EPF on her face seven years after having nose and chin augmentation with subcutaneous silicone injections.     

Prevalence of autoantibodies in patients with endemic pemphigus foliaceus (fogo selvagem)

Objective The aim of the present study was to investigate a broad spectrum of autoantibodies in patients with endemic pemphigus foliaceus (EPF)—fogo selvagem—and to determine the possible association between EPF and other autoimmune diseases.Materials and methods Indirect immunofluorescence was used to test 120 patients with EPF and 200 healthy controls for the presence of the following autoantibodies: anti-desmoglein-1 (APF), anti-neutrophil cytoplasmic (ANCA), anti-smooth muscle (SMA), anti-mitochondrial (AMA), anti-nuclear (ANA), anti-liver kidney microsomal (LKM), anti-gastric parietal cells (GPCA) and anti-thyroid microsome (TMA).Results APF antibodies were detected in 62.5% of the patients (75/120), ANA and SMA in 0.8% (1/120), and TMA in 1.6% (2/120). None of the patients was positive for ANCA, AMA, LKM or GPCA. In the control group, a positivity of 2% was observed for SMA (4/200), 1.5% for TMA (3/200), and 0.5% (1/200) for ANA and GPCA. None of the controls was positive for APF, LKM, AMA or ANCA.Conclusions The prevalence of the autoantibodies ANA, SMA, AMA, GPCA, LKM and ANCA in patients with EPF was similar to that observed in the control group. No association with clinical or laboratory manifestations of other concomitant autoimmune diseases was observed in EPF patients. These results confirm the concept that EPF is an organ-specific autoimmune disease.     

Eosinophilic pustular folliculitis associated with hematological disorders: A report of two cases and review of Japanese literature

Eosinophilic pustular folliculitis (EPF) occurs in patients with hematological disorders. However, clinical information about hematological disorder‐associated EPF is scarce. We report two cases of EPF associated with mantle cell lymphoma and reviewed the available published work on Japanese cases. We identified a total of 23 Japanese cases, including the two cases reported here, who had hematological disorder‐associated EPF. Fourteen cases were associated with treatment for hematological malignancies (transplantation‐related EPF) and nine cases were associated with hematological malignancies themselves (hematological malignancy‐related EPF). Although the skin eruption was clinically indistinguishable between the two subtypes, transplantation‐related EPF occurred on the face and trunk of young and middle‐aged men and women, whereas hematological malignancy‐related EPF occurred mostly on the face of older men. Peripheral blood eosinophilia was more frequently observed in transplantation‐related EPF. These observations suggest variations among patients with EPF associated with hematological disorders.     

Facial pustules due to drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms may histopathologically mimic eosinophilic pustular folliculitis: A case report

Pustules with facial and/or neck edema is one characteristic feature of drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) at the early stage. Although several retrospective histopathologic studies on DIHS/DRESS have been reported, the detailed histopathologic findings of facial pustules for DIHS/DRESS are unavailable. We herein report a case of DIHS/DRESS with facial pustules that was histopathologically similar to eosinophilic pustular folliculitis (EPF). Eosinophilic infiltration into expanded follicles and sebaceous glands, which is highly characteristic of EPF, was detected in pustules due to DIHS/DRESS in this case. There are numerous pathophysiological similarities between DIHS/DRESS and EPF, which may cause their histopathologic similarity. Our findings suggest that facial pustules of DIHS/DRESS may histopathologically mimic EPF.     

Comparative study of autoantigen profile between Colombian and Brazilian types of endemic pemphigus foliaceus by various biochemical and molecular biological techniques

BACKGROUND: Besides Brazilian endemic pemphigus foliaceus (EPF), we have described another focus of EPF in Colombia. Our previous study suggested that Colombian EPF seemed to react various plakin family proteins, such as envoplakin, periplakin and BP230. OBJECTIVE: To further characterize the Colombian EPF and study the difference from Brazilian EPF, we examined the antigen profile of the two types of EPF. METHODS AND RESULTS: Immunoblotting using normal human epidermal extracts revealed that 38% Colombian EPF sera and 25% Brazilian EPF sera showed IgG antibodies reactive with desmoglein (Dsg) 1, pemphigus foliaceus antigen. The sera of both types of EPF showed protein bands co-migrating with plakin family proteins, particularly periplakin. Immunoblotting analyses using recombinant proteins of various domains of envoplakin, periplakin and BP230 revealed that a considerable number of Colombian EPF sera reacted with recombinant proteins of periplakin, while only few Brazilian sera reacted with some of the recombinant proteins of any plakins. Enzyme-linked immunosorbent assay (ELISA) for Dsg1 and Dsg3 showed that Dsg1 was reacted by almost all sera of both types of EPF. However, unexpectedly, while none of Colombian EPF sera reacted with Dsg3, about half of Brazilian EPF sera reacted with Dsg3. CONCLUSION: These results suggested that the Colombian EPF is basically similar to Brazilian EPF in terms that major antigen is Dsg1, but there were some different antigen profiles between the two types of EPF.     

Eosinophilic pustular folliculitis: A proposal of diagnostic and therapeutic algorithms

Eosinophilic pustular folliculitis (EPF) is a sterile inflammatory dermatosis of unknown etiology. In addition to classic EPF, which affects otherwise healthy individuals, an immunocompromised state can cause immunosuppression‐associated EPF (IS‐EPF), which may be referred to dermatologists in inpatient services for assessments. Infancy‐associated EPF (I‐EPF) is the least characterized subtype, being observed mainly in non‐Japanese infants. Diagnosis of EPF is challenging because its lesions mimic those of other common diseases, such as acne and dermatomycosis. Furthermore, there is no consensus regarding the treatment for each subtype of EPF. Here, we created procedure algorithms that facilitate the diagnosis and selection of therapeutic options on the basis of published work available in the public domain. Our diagnostic algorithm comprised a simple flowchart to direct physicians toward proper diagnosis. Recommended regimens were summarized in an easy‐to‐comprehend therapeutic algorithm for each subtype of EPF. These algorithms would facilitate the diagnostic and therapeutic procedure of EPF.     

Eosinophilic Pustular Folliculitis in Children after Stem Cell Transplantation: An Eruption Distinct from Graft‐Versus‐Host Disease

Eosinophilic pustular folliculitis (EPF) is a rare cutaneous disorder that typically occurs in three clinical contexts: men, individuals who are immunosuppressed or have human immunodeficiency virus, and infants. A fourth subtype occurring 2 to 3 months after hematopoietic stem cell transplantation (HSCT) has recently been described in several adults. We report two cases of EPF arising in children after HSCT. It is important to recognize this form of EPF after HSCT and differentiate it from graft‐versus‐host disease since it responds readily to topical steroids and appears to have an excellent prognosis.     

Eosinophilic pustular folliculitis: The transition in sex differences and interracial characteristics between 1965 and 2013

Eosinophilic pustular folliculitis (EPF) is characterized by a non‐infectious infiltration of eosinophils in the hair follicles. It has three variants: (i) classic EPF; (ii) immunosuppression‐associated EPF, which herein is subdivided into HIV‐associated (IS/HIV) and non‐HIV‐associated (IS/non‐HIV); and (iii) infancy‐associated EPF (I‐EPF). The rarity of EPF has hindered our understanding of this entity. To examine the characteristics of EPF, with respect to age, sex, race, and chronology, published in case reports to date, we queried PubMed using the following terms: (“eosinophilic pustular folliculitis” [All Fields] OR “eosinophilic folliculitis” [All Fields]) AND (“1965/1/1” [PDAT]: “2013/12/31” [PDAT]). Additional Japanese cases were collected from Igaku Chuo Zasshi through Ichushi‐Web, JDream III, and secondhand quotations from domestic periodicals published in Japan. Proceedings were excluded. The PubMed search produced 275 citations containing 358 cases of EPF (224 men, 132 women, and two of unspecified sex); these cases involved classic EPF (101 Japanese and 81 non‐Japanese), IS/HIV (4 Japanese and 85 non‐Japanese), IS/non‐HIV (4 Japanese and 20 non‐Japanese), and I‐EPF (4 Japanese and 59 non‐Japanese). Ichushi generated an additional 148 citations containing 207 cases of Japanese (148 men and 59 women), which included cases of classic EPF (181 cases), IS/HIV (14 cases), IS/non‐HIV (9 cases), and I‐EPF (3 cases). There was no sex difference in the classic EPF cases reported between 2003 and 2013, whereas IS/HIV, IS/non‐HIV, and I‐EPF were predominated by men. There is room for reconsideration of sex differences, particularly with regard to classic EPF. The rarity and specificity of I‐EPF in Japan may reflect a state of uncertainty about this entity.     

HIV seronegative eosinophilic pustular folliculitis successfully treated with doxicycline

Eosinophilic pustular folliculitis (EPF) is an unusual disease, first described in adult East Asians in 1970 by Ofuji. It is characterized by follicular papules and pustules tending to coalesce and form plaques involving the trunk, face and extremities. In recent years, it has been often associated with human immunodeficiency virus (HIV) infection or with immunosuppressed and/or oncohaematological patients. EPF has been described in immunocompetent adult caucasian patients only occasionally. The diagnosis requires clinical and microbiological features such as sterile folliculitis and histopathological findings characterized by folliculitis and perifolliculitis with eosinophilic infiltrate. We describe an HIV seronegative caucasian male with EPF, allergic to non-steroidal anti-inflammatory drugs and indomethacin, treated with oral doxicycline. The treatment led to the complete remission of the lesions within 2 months.