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: 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.     

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 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: 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.     

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.     

Epidemiological survey of patients with pustular psoriasis in the Japanese Society for Psoriasis Research from 2017 to 2020

The Japanese Society for Psoriasis Research (JSPR) has been conducting annual epidemiological surveys of patients with pustular psoriasis in Japan since 2017. This study aimed to conduct a recent epidemiological analysis of patients with pustular psoriasis who were enrolled in the JSPR from 2017 to 2020. A total of 291 patients from 131 medical institutions were enrolled, of which 47.4% (138 cases) were males and 52.6% (153 cases) were females. The mean ± standard deviation (SD) age of the patients was 57.4 ± 20.3 years (males, 61.2 ± 17.3 years; females, 54.1 ± 22.1 years). The mean ± SD age of the patients at disease onset was 48.5 ± 22.5 years (males, 50.8 ± 20.6 years; females, 46.4 ± 24.0 years). The types of pustular psoriasis observed included the von Zumbusch type (59.8%), annular pustular psoriasis (8.2%), impetigo herpetiformis (6.5%), and acrodermatitis continua of Hallopeau (4.8%), of which, the majority of the patients with impetigo herpetiformis were female. Among the patients, 58.4% were treated with oral medications and 44.0% were treated with biologics. The most common oral medication prescribed was etretinate (52.4%), followed by corticosteroids (24.7%) and cyclosporin (22.9%). The most common biologics used were IL-17 inhibitors (ixekizumab [28.1%] and secukinumab [22.7%]), followed by tumor necrosis factor (TNF) inhibitors (infliximab [15.6%]) and IL-23 inhibitors (guselkumab [14.8%] and risankizumab [10.2%]). This survey thus provides new and significant information regarding the recent perspective of pustular psoriasis, such as patient characteristics and treatment trends, in Japan.     

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.     

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.     

Eosinophilic pustular folliculitis starting initially only with palmoplantar pustular lesions. Report of a case and review of the literature.

We report a 23-year-old Japanese male with eosinophilic pustular folliculitis (EPF) that had started with palmoplantar rash. Only when follicular pustules appeared on the bilateral cheek 31 months later, we revised our initial diagnosis of pustulosis palmaris et plantaris (PPP) to EPF, and all the skin eruptions cleared mostly with indomethacin. A review of the Japanese literature for the past 20 years disclosed that in 207 cases of EPF so far reported, palmoplantar pustular lesion was noted in 38 (18%). Among them, in 16 cases (8%) the skin lesions started first from the palmoplantar region with the average period of 26 months until the appearance of other eruptions of EPF. None of them was diagnosed as EPF when skin lesions were localized only to the palmoplantar region. When we find pustules on the palmoplantar region, we should suspect the possibility of early lesions of EPF as well as PPP. Histopathologic demonstration of multilocular pustules located in the upper epidermis containing numerous eosinophils in the palmoplantar pustular lesions, together with the dramatic therapeutic response to indomethacin greatly favor the diagnosis 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 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 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.     

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.     

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.     

Epidermodysplasia verruciformis.--Report of a case and genetic consideration on the Japanese cases.

Thirty three Japanese cases recorded in the last 10 years are reviewed with an additional case of a 57-year-old Japanese woman with typical eruptions and cutaneous malignancies. Familial occurrence and parental consanguinity were seen in at least 30.0% and 26.7% of the cases respectively, further suggesting the recessive mode of inheritance which affects males and females almost equally. Cutaneous malignancy was seen in 48.5% of these patients with an average age of 35.3 yrs.     

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.     

HLA‐C*12:02 is a susceptibility factor in late‐onset type of psoriasis in Japanese

Psoriasis is thought to be a multifactorial disease triggered by both genetic and environmental factors. The HLA‐C locus on chromosome 6p21.33 remains the strongest susceptibility candidate locus in psoriasis. The strong association between psoriasis and the HLA‐Cw6 allele has been well documented in various races. It is known that psoriatic patients with early onset are more likely to be familial and associated with HLA‐Cw6. Familial occurrence of Japanese psoriasis is smaller than other populations. Furthermore, males are predominant over females in Japanese psoriasis. We investigated the relation between HLA‐C alleles and age of onset, and in each gender for Japanese psoriasis, and discuss male predominance in the incidence of psoriasis in Japan. Four hundred forty six unrelated Japanese patients with psoriasis vulgaris and 557 sex‐ and age‐matched unrelated Japanese healthy controls were investigated by genotyping. We confirmed the association between early‐onset type of psoriasis with HLA‐C*06:02 allele in Japanese. In addition, we detected the association between the late‐onset type of psoriasis and the HLA‐C*12:02 allele in Japanese. No significant differences in allele frequency were observed between females and males. Our results suggest that there is no genetic factor effect on male predominance in Japanese. In contract, the effect of environmental risk factors on the onset of Japanese psoriatic patients is stronger in males than in females. As a result, male predominant in psoriasis may occur in Japan.     

Effect of monochromatic excimer light on palmoplantar pustulosis: A clinical study performed in a private clinic by a dermatological specialist

Palmoplantar pustulosis (PPP) is currently treated with various modalities, including excimer light, a form of ultraviolet lamp. This study reports effect of excimer light treatment in 34 Japanese PPP patients treated at a private clinic by one doctor, who was certified as a dermatological specialist by the Japanese Dermatological Association. The statistical analyses were performed upon a collaborative basis with faculties in universities. Disease response scores were determined by response to excimer light treatment. Scores of 1, 2, 3 or 4 were assigned to patients whose palmoplantar pustular psoriasis area and severity index (PPPASI) decreased to 25% or less, 25.1–50%, 50.1–75% or more than 75.1% of pretreatment PPPASI, respectively. In this study, 44.1% PPP cases had scores of 1 or 2, and considered good responders to excimer light treatment. There were no statistical differences between males and females, and between older (≥40 years) and younger groups (≤39 years) in terms of disease response score. Disease duration did not show any significant difference among these scores. Treatment times, total amount of ultraviolet and total treatment duration showed significant differences between score 1 and score 4 groups (P = 0.0164, =0.0137 and =0.0267, respectively). Particular interest was paid to smoking habits. Smoking in male patients was significantly higher than that in female patients (P = 0.0169). There was no statistical difference between smokers and non‐smokers in terms of response to excimer light. In conclusion, this study suggested that excimer light is useful for both initial regimen and suppression of exacerbation in treatments of PPP.