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.     

Eosinophilic pustular folliculitis. Studies on possible chemotactic factors involved in the formation of pustules

Eosinophilic pustular folliculitis (EPF) is a dermatosis of unknown aetiology, characterized by repeated development of pruritic follicular papulopustules with a tendency to form an annular configuration on the face and other seborrhoeic areas, and by palmoplantar pustular lesions in one-fifth of the patients. Both types of lesions are infiltrated mainly by eosinophils with some polymorphonuclear leukocytes (PMN). To elucidate the mechanisms underlying pustule formation, we studied the chemotactic activity for leukocytes of the skin surface lipids (SSL) obtained from seborrhoeic areas. No specific chemotactic activity was detectable in stored SSL from patients with EPF. However, fresh SSL collected from the seborrhoeic areas of normal adults contained chemotactic substances for eosinophils and PMN which were labile on storage in air. In stratum corneum extracts from palmoplantar lesions of patients with EPF we demonstrated the presence of a 13000 molecular weight chemoattractant factor for PMN, the activity of which was partially inhibited by antiserum against C5a, and a low molecular weight lipid-soluble chemotactic factor for eosinophils, the activity of which was also lost on storage in air. Our findings suggest that these chemotactic factors play a role in the production of the characteristic pustular lesions of 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.     

Palmoplantar pustular psoriasis: successful therapy with efalizumab after non-response to infliximab

Palmoplantar pustular psoriasis (PPP) is a chronic inflammatory skin condition mainly characterized by recurrent eruptions of sterile pustules on erythematous skin; hyperkeratosis and fissures on the palms and soles are additional clinical features. Treatment options for PPP are unsatisfactory. We present a patient with a typical course of PPP that had previously received a broad range of topical and systemic antipsoriatic therapies. They all had to be discontinued due to ineffectiveness or side effects. Being aware of the high efficacy of infliximab in generalized pustular psoriasis, we initiated this therapy. An initial improvement was followed by a substantial flare after 7 months, during which a combination treatment of infliximab with methotrexate was administered. Only subsequent monotherapy with efalizumab led to complete clearing up of PPP after 10 to 12 weeks of treatment without any adverse effects. This indicates that efalizumab is potentially effective in PPP.     

Interleukin‐17 receptor A blockade with brodalumab in palmoplantar pustular psoriasis: Report on four cases

Palmoplantar pustular psoriasis, also termed palmoplantar pustulosis (PPP), is a rare disease affecting the palmoplantar regions characterized by sterile, yellow to brown pustules mostly on erythematous skin. PPP is related to a high burden due to painful, impaired and stigmatizing character. Several isoforms of interleukin (IL) have been implicated in its pathophysiology. Here, we report on four patients with PPP treated with the novel IL‐17 receptor A blocker brodalumab, in whom this therapy was not successful or showed moderate improvement combined with adverse events.     

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.     

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.     

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.     

Exanthematic type of pustular psoriasis consisting of two types of pustular lesion.

A 35-year-old female developed generalized pustules within a short period of time. Clinically, two distinct types of pustules were observed, viz. erythematous patches studded with crops of small pustules, and isolated large pustules with a red halo. Histologically, the former were subcorneal spongiform pustules, whereas the latter were unilocular pustules involving the hair follicular infundibulum or a subcorneal unilocular pustule on the palmo-plantar skin. On the basis of the sudden appearance of the pustules without any pre-existing lesions of psoriasis and the histological findings of the spongiform pustules, we made a diagnosis of the exanthematic type of pustular psoriasis. The lesions responded in a dose-dependent fashion to oral cyclosporin.     

Cutaneous pustular leukemoid reactions in trisomy 21

We report two neonates with Down syndrome and postnatal leukemoid reactions who developed acute widespread pustular eruptions. The white blood cell (WBC) counts on the first day of life were markedly elevated, with blasts seen on examination of the peripheral blood smear. The skin eruptions progressed and became pustular. Viral and bacterial cultures were negative. Skin examination revealed pustules on an erythematous base on the cheeks, shoulders, trunk, and proximal extremities. Skin biopsy specimens showed an intraepidermal pustule with an inflammatory infiltrate including neutrophils, eosinophils, and mononuclear cells. The mononuclear cells had atypical, immature-appearing nuclei. In patient 1, these cells were strongly myeloperoxidase positive on immunohistochemistry, indicating myeloid lineage. In patient 2, these cells were CD3-positive T cells. Patient 1 received a 5-day infusion of continuous cytarabine (ara-C) secondary to high WBC counts and symptomatic hyperviscosity. During therapy, the high WBC count and the pustules resolved. The lesions of patient 2 improved with topical mometasone furoate and resolved as her WBC count decreased. Recently, similar cases have been reported. Transient myeloproliferative disorders, or leukemoid reactions, should always be considered when newborns with Down syndrome or trisomy 21 mosaicism develop a pustular eruption.     

Eosinophilic pustular folliculitis (Ofuji's disease): indomethacin as a first choice of treatment

Eosinophilic pustular folliculitis (EPF) is characterized by erythematous patches of large follicular papules and pustules involving mainly the face. Although various treatments have been attempted for EPF, including systemic and topical steroid, diaphenylsulphone, colchicine, minocycline as well as UVB phototherapy, there is no consensus on the first choice of treatment. We report a typical case and summarize 25 patients with EPF treated in our hospital between 1978 and 1998. Indomethacin was most frequently used (12/25) and showed clinical improvement in the majority of the cases (11/12). The effect of indomethacin was usually observed within 1--2 weeks after initiation of treatment. Decrease of peripheral blood eosinophils accompanied the clinical improvement. Thus, indomethacin should be considered as a first choice of treatment for EPF.     

Novel IL36RN mutation in a Japanese case of early onset generalized pustular psoriasis

Generalized pustular psoriasis is a distinct type of psoriasis characterized by recurrent febrile attacks with disseminated subcorneal pustules on generalized skin rashes. Recently, homozygous and compound heterozygous mutations of the IL36RN gene, which encodes the anti‐inflammatory cytokine interleukin (IL)‐36 receptor antagonist, were identified in familial and sporadic cases of various ethnicities with generalized pustular psoriasis. Here we report a 39‐year‐old Japanese male patient who had suffered from repeated attacks of generalized pustular psoriasis since infancy with intervals of several years. At presentation, erythematous lesions with a few pustules were found only on some parts of the body and controlled with topical corticosteroids. An analysis of the IL36RN gene revealed compound heterozygous mutations of c.28C>T and c.368C>T. While the former mutation causing the premature termination p.Arg10X is recurrent in Japanese cases, the latter missense mutation causing p.Thr123Met substitution is novel, but another mutation in the same position has been reported in one Japanese case. Our report further supports the presence of the Japanese‐specific hot spots in the IL36RN gene, 28C and 368C, and suggests the functional significance of Thr123. This special type of generalized pustular psoriasis caused by IL36RN mutations has been designated as deficiency for IL‐36 receptor antagonist, a new hereditary autoinflammatory disease, and its phenotypes have emerged to include other related pustular disorders, palmoplantar pustulosis, acrodermatitis continua of Hallopeau, and acute generalized exanthematous pustulosis. The genetic analysis of the cases with these diseases would be important for establishment and application of the specific treatments targeting the IL‐36 signaling.     

Two cases of eosinophilic pustular folliculitis associated with parasitic infestations

Two patients presented with papular eruptions that could not be diagnosed clinically. Biopsies of these lesions showed eosinophilic pustular folliculitis (EPF). Both cases were subsequently found to have infestations: one as a result of cutaneous larva migrans was successfully treated with ivermectin and the other caused by scabies mites was successfully treated with topical pyrethrin. The two cases of EPF presented emphasize the need for careful clinicopathological correlation to determine the cause.     

Generalized pustular drug eruptions: confirmation by in vitro tests

Background Generalized pustular eruptions are characterized by acute onset of aseptic pustules in febrile patients with leukocytosis after exposure to the offending drug. They have been regarded as uncommon manifestations of adverse drug reactions. Until now few confirmation studies have been carried out. Objective Our purpose was to describe a series of patients with generalized pustular drug eruption. The diagnosis and etiological role of drugs in these cases was confirmed by two in vitro tests, namely the macrophage migration inhibitory factor (MIF) and the mast cell degranulation (MCD) tests. Methods The clinical, pathological and laboratory findings in six patients with generalized pustular eruption were studied prospectively. The MIF and MCD tests were performed with the drugs taken by the patients. Results The dermatological manifestations included numerous pustules on large erythematous areas, papules and erythema multiforme-like lesions. The pustular eruption developed between 12 h and 5 days after the administration of the provoking drug. The histopathological changes were characterized by subcorneal pustules, papillary edema and mixed cell inflammatory infiltrate. In two biopsies the infiltrate displayed numerous eosinophils. Laboratory investigations revealed leukocytosis with neutrophilia (4 of 6 patients) and eosinophilia and hyperimmunoglobulinemia E (2 of 6 patients).MCD tests with the suspected drugs (Ampicillin, Cefazolin, Tetracycline, Griseofulvin, Enalapril Maleate) were positive in all patients. Positive MIF results were seen in five of the six patients. Withdrawal of the drug led to fast recovery. Conclusion The diagnosis of pustular drug eruptions depends on circumstantial evidence, some characteristic clinico-pathological findings and exclusion of alternative diagnoses of other disseminated pustular eruptions. In vitro tests, namely MIF and MCD tests, are a useful diagnostic aid in the identification of the offending drugs.     

Eosinophilic pustular folliculitis (Ofuji's disease) without macroscopic pustules

Background Eosinophilic pustular folliculitis (EPF), first described by Ofuji et al. in 1970, is a rare dermatosis characterized by pruritic papules and pustules on circinate erythematous plaques with eosinophilic infiltration in and around the hair follicle. Methods and results We report three cases of EPF that showed no macroscopic pustules during the total observation period. Histopathological examination revealed eosinophilic infiltration in and around the hair follicle in the lower dermis and subcutis. Conclusions EPF consists of clinical variants, one of which lacks obvious pustules.     

Alterations of surface receptors on intralesional neutrophils in pustular psoriasis and palmo-plantar pustulosis

Alterations of binding capacity of surface IgG-Fc and complement receptors were demonstrated in polymorphonuclear neutrophils (PMNs) obtained from the pustular lesions of psoriasis. A marked decrease of C3 receptors, but not of IgG-Fc, was found in PMNs from the lesions of palmo-plantar pustulosis (PPP) and bacterial pustules. PMNs from pustular lesions of psoriasis exhibited only a slight decrease in the number of C3 receptors. No significant decrease in membrane receptors was noted in circulating PMNs from psoriatic patients. We suggest that mechanisms of formation of aseptic subcorneal pustules, mediated by PMN membrane receptors for C3 fragments, are different in pustular psoriasis and PPP.     

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.     

Subcorneal pustular dermatosis in the pediatric age

Subcorneal pustular dermatosis is a rare pustular eruption which occurs mainly in middle-aged women and rarely during childhood. We report a case of a 15-year-old female with a 4-year history of pustular lesions on the proximal region of the upper limbs with subsequent impairment of the trunk. Physical examination revealed small pustules distributed on the trunk and proximal region of the limbs. Histopathology showed a subcorneal pustule and direct immunofluorescence for IgA, IgM, IgG and fibrinogen was negative, confirming the diagnosis of subcorneal pustular dermatosis. The patient was treated with dapsone with good clinical response after one month. Subcorneal pustular dermatosis is a rare condition and there are only isolated cases reported in the literature in pediatric patients. Thus, we discuss the main clinical aspects and treatment response of this condition during childhood.     

Pustular skin disorders: diagnosis and treatment

The differential diagnosis for pustular skin disorders is extensive. The distribution of the lesions and the age of the patient are characteristics that may provide strong clues to the etiology of cutaneous pustular eruptions. In adults, generalized pustular dermatoses include pustular psoriasis, Reiter's disease and subcorneal pustular dermatosis. Medications can cause generalized pustular eruptions, such as in the case of acute generalized exanthematous pustulosis; or more localized reactions, such as acneiform drug eruptions, which usually involve the face, chest and back. Localized pustular eruptions are seen on the hands and feet in adults with pustulosis palmaris et plantaris and acrodermatitis continua (both of which may be variants of psoriasis); on the face in patients with acne vulgaris, rosacea, and perioral dermatitis; and on the trunk and/or extremities in patients with folliculitis. A separate condition known as eosinophilic folliculitis occurs in individuals with advanced human immunodeficiency disease. Severely pruritic, sterile, eosinophilic pustules are found on the chest, proximal extremities, head and neck. Elevated serum immunoglobulin E and eosinophilia are often concurrently found. In neonates, it is especially important to make the correct diagnosis with respect to pustular skin disorders, since pustules can be a manifestation of sepsis or other serious infectious diseases. Generalized pustular eruptions in neonates include erythema toxicum neonatorum and transient neonatal pustular melanosis, both of which are non-infectious. Pustules are seen in infants with congenital cutaneous candidiasis, which may or may not involve disseminated disease. Ofuji's syndrome is an uncommon generalized pustular dermatosis of infancy with associated eosinophilia. As in adults, neonates and infants may develop acne or scabies infestations. In this article, we review the most common pustular dermatoses and offer a systematic approach to making a diagnosis. We also report the most up-to-date information on the treatment of these various cutaneous pustular conditions.