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.     

Expression of neuronal nitric oxide synthase in dermal infiltrated eosinophils in eosinophilic pustular folliculitis

Nitric oxide (NO) is produced by a wide variety of human cells and affects physiological and pathophysiological processes. In this study, we demonstrated for the first time that neuronal NO synthase (NOS) is expressed in eosinophils infiltrating into the dermis and follicular epidermis in eosinophilic pustular folliculitis (EPF). EPF is a cutaneous inflammatory follicular disorder first described in Japan. The clinical and histological features of EPF are characterized by erythematous papules, infiltration of numerous eosinophils, and a spongiotic appearance of the follicular epidermis, but the pathophysiology of EPF remains unclear. Our results suggest that NO produced from eosinophils plays an important part in the pathogenesis of EPF. Furthermore, we speculate that NOS inhibitors may be useful in the management of 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 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.     

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 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.     

北京协和医院29 987例皮肤活检组织的临床病理诊断构成

【摘要】 目的 分析北京协和医院皮肤活检组织的疾病构成及临床和病理诊断情况。方法 回顾北京协和医院皮肤科2010年6月至2018年11月采用皮肤组织病理检查的29 987例患者,分析组织病理和诊断情况。结果 根据病理诊断结果,将确诊的皮肤疾病分为33大类,242种。常见的疾病类别分别为表皮肿瘤（2 931例,9.77%）、结缔组织病（2 809例,9.37%）、黑素细胞性肿瘤（2 078例,6.93%）、红斑鳞屑脓疱性皮肤病（1 376例,4.59%）、苔藓样皮肤病（1 291例,4.31%）、变态反应和湿疹类（1 282例,4.28%）及感染性疾病（1 156例,3.86%）等。常见疾病为硬皮病（1 887例,6.29%）、色素痣（1 755例,5.85%）、脂溢性角化（1 136例,3.79%）、湿疹（1 089例,3.63%）、银屑病（881例,2.94%）、扁平苔藓（867例,2.89%）、红斑狼疮（638例,2.13%）、天疱疮（549例,1.83%）和基底细胞癌（501例,1.67%）等。扁平苔藓、大疱性类天疱疮、环状肉芽肿、嗜酸性粒细胞增多性皮病等的临床诊断不符合率高,与病理诊断的一致率较低。结论 本院皮肤活检组织中表皮肿瘤、结缔组织病、黑素细胞性肿瘤、红斑鳞屑脓疱性皮肤病、苔藓样皮肤病、变态反应和湿疹类占比高。部分皮肤病临床诊断与病理诊断一致率低,对此类疾病需提高认识。     

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.     

Eosinophilic pustular folliculitis following autologous peripheral blood stem-cell transplantation

We describe a case of eosinophilic pustular folliculitis (EPF) occurring after autologous peripheral blood stem-cell transplantation for non-Hodgkin's lymphoma and successfully treated with oral and topical indomethacin. Including ours, the reported cases of EPF with HIV-negative hematological disease have shown clinical features similar to those of HIV-associated EPF, however the prognosis is better than that for HIV-associated EPF, which usually shows a persistent course. EPF with HIV-negative hematological disease can be classified as a unique group in EPF.     

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.     

Eosinophilic pustule smear in the diagnosis of pediatric post-transplant eosinophilic folliculitis

Hematologic-associated eosinophilic pustular folliculitis is a subtype of eosinophilic pustular folliculitis (EPF) which develops in patients with underlying hematological malignancies after treatment with chemotherapy, bone marrow transplant (BMT), or stem cell transplant (SCT). Few cases of hematological-associated EPF have been reported in pediatric patients. Skin biopsy is considered the gold standard for diagnosis. We describe a case in which Wright staining of a pustule smear for eosinophils provided data to rapidly support a clinical diagnosis of hematologic-associated EPF.     

Eosinophil-infiltrating folliculitis in childhood--report of a case

A 5-year-old Japanese girl developed follicular pustules with erythematous plaques on the lower extremities. The histopathology was compatible with eosinophilic pustular folliculitis (EPF). However, the clinical findings were not typical of EPF; the pustules did not appear in crops, the pustules became ulcers, and the skin lesions appeared exclusively on non-seborrheic areas.     

Neonatal eosinophilic pustular folliculitis

Eosinophilic pustular folliculitis (EPF) of infancy is a rare disorder which may begin in the neonatal period and cause considerable parental anxiety. It must be distinguished from other causes of a pustular eruption in neonates, including infection and erythema toxicum neonatorum, and rare disorders such as transient neonatal pustular melanosis, infantile acropustulosis and Langerhans' cell histiocytosis. Skin smears and occasionally skin biopsy may be necessary to reach a diagnosis. We report a case of a Caucasian child with an unusually early onset of EPF in the first day of life. We wish to emphasize the importance of recognizing this self-limiting condition in order to prevent inappropriate antimicrobial treatment.     

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.     

脓疱性银屑病76例临床分析

目的：分析脓疱性银屑病的临床特征。方法：对76例脓疱性银屑病患者按照国际上通行的分类方法进行诊断和分类，并对其病史资料、临床特征和治疗经过进行分析。结果：该76例脓疱性银屑病在同期就诊的银屑病患者中占8．6%，其中以局限性居多．占71．0％．主要累及掌跖部位；泛发性病例中5种临床亚型均各有2～6例患者，表现为程度不一的红斑、脓疱和鳞屑根据不同的皮疹特点给予窄谱中波紫外线(NB-UVB)、长波紫外线(UVA）、维A酸等综合治疗取得较为满意的效果，有效率为49．2％结论：脓疱性银屑病的临床表现和治疗反应在不同患者间差异较大。新的分类方法对指导临床实践具有积极意义。     

Eosinophilic Pustular Folliculitis in Infancy: Report of Two New Cases

Eosinophilic pustular folliculitis (EPF) is a cutaneous inflammatory follicular disorder of unknown etiology. The diagnosis is made on the basis of clinical and histopathologic features. We describe two patients who had recurrent episodes of pruritic follicular papular and pustular lesions on the face, extremities, and trunk. The eruptions lasted for 1 month with intermittent remissions. Laboratory tests disclosed no infectious or parasitic etiology in patient 2. In patient 1 we isolated methicillin-resistant Staphylococcus aureus in a blood culture. He had sepsis with lung and liver involvement. EPF is a self-limited dermatosis. On occasion, skin lesions may become superinfected, resulting in localized pyoderma or rarely systemic infection (sepsis). Histologically both of our patients showed a moderate mixed inflammatory infiltrate with numerous eosinophils centered around hair follicles. Their lesions responded well to topical corticosteroids.     

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.     

Eosinophilic pustular folliculitis: report of seven cases in Thailand

Seven cases of eosinophilic pustular folliculitis (EPF) were diagnosed at the Institute of Dermatology within the seven years from 1989-1996. There were 4 males and 3 females, age 24-44 years, with durations of the disease before diagnosis ranging from 3 months to 5 years. The face was the most commonly involved area. Lesions also occurred simultaneously on other sites including the chest, trunk, scalp, and palmoplantar areas. Diagnosis was made from clinical features, hematologic examinations, and histopathologic pictures. Topical piroxicam gel, 0.5%, and oral indomethacin gave good results; some lesions subsided within a few days, and the remissions lasted for four months to five years.