Pruritic plaque with pustules on the nose and cheeks

The patient
A 16-year-old female presented herself to us with a 2-month history of pruritic, erythematous, annular plaques studded with papules and pustules on her face, particularly on the malar and nasal areas (Fig. 1). The lesions were enlarged by peripheral extension and central clearing was noted. The patient had been diagnosed previously with seborrheic dermatitis and was treated with topical steroids and antifungals with minimal improvement.

Cutaneous examination revealed an asymmetric, well-circumscribed, erythematous, and edematous plaque on the nasal area and both cheeks with central clearing and overlying fine scales. Scattered pustules and papules were noted on the surface of the plaque.

Fig. 1: Erythematous, edematous plaque on the nasal area and both cheeks with overlying fine scales and scattered pustules and papules.

Histopathology
A 4 mm punch biopsy was taken from the periphery of the lesion (Figs. 2A–K). What is your diagnosis?

Figs. 2A – K: Histopathology.

Answer
Ofuji's disease (eosinophilic pustular folliculitis)

Histopathologic examination of a biopsy specimen taken from the periphery of the lesion showed focal parakeratosis of the stratum corneum. There was spongiosis of the epidermis with exocytosis of eosinophils. The dermis revealed a moderately dense perivascular and periadnexal inflammatory infiltration consisting of lymphocytes, numerous eosinophils, and some neutrophils. There was spongiosis of the follicular epithelium and telangiectasia of surrounding blood vessels. Noteworthy was the prominent eosinophilic infiltration of the seboglandular ducts and sebaceous glands in which eosinophilic abscesses were observed. Periodic acid-Schiff staining for fungus was negative.

Laboratory examination showed normal results of complete blood count, urinalysis, hepatic and renal function tests, serum glucose, erythrocyte sedimentation rate, and antinuclear antibody titer. Culture from pustules showed no bacterial growth. A potassium hydroxide (KOH) smear was negative for spores and hyphae, and there was no growth observed on fungal culture.
These findings together enabled a diagnosis of Ofuji's disease to be made.

Comment
The classic form of eosinophilic pustular folliculitis (Ofuji's disease) was initially described among the Japanese and Chinese as a rare dermatosis characterized by recurrent outbreaks of pruritic, sterile, papulopustular skin lesions with tendency to form circinate plaques.[1 ] The lesions have a tendency to extend peripherally with central clearing and resolve with postinflammatory hyperpigmentation. The seborrheic areas are the most frequently affected sites although the extremities, mucous membranes, and palms and soles may be involved. [1–4 ] The face is affected in 95% of cases and is often the first site of involvement. [5,6 ] Peripheral eosinophilia is observed in 50% of cases but normalizes once the skin lesions resolve. [6 ] The etiology of eosinophilic pustular folliculitis remains unknown. Various immunological dysfunctions have been reported in some patients, but this is not a consistent feature. [7 ]

Eosinophilic pustular folliculitis associated with HIV infection has been regarded by some authors as a separate clinical entity as it usually presents as intensely pruritic, erythematous, urticarial papules, which are located predominantly on the trunk. [8 ]

Eosinophilic pustular folliculitis has also been described in association with non-Hodgkin's lymphoma, Hodgkin's lymphoma, leukemia, myelodysplastic syndrome, and bone marrow transplantation, in which the clinical presentations were identical to those seen in HIV patients. [9–13 ]

Eosinophilic pustular folliculitis in infancy has also been observed but also seems to be a different clinical variant because of constant and predominant involvement of the scalp. [14,15 ] Some authors have called into question whether this latter condition really represents a distinctive disease or whether patients diagnosed with it suffer from other diseases such as scabies and arthropod reactions. [16 ]

Drug-induced eosinophilic pustular folliculitis has been documented with allopurinol, timepidium bromide, minocycline, indeloxazine hydrochloride, and carbamazepine. [5,17–19 ]

The histologic pattern of eosinophilic pustular folliculitis is characterized by a combination of a perivascular and interstitial eosinophil-rich infiltrate and an eosinophilic-rich pustular infundubulitis. The follicular infundibulum and outer root sheaths usually show intracellular and intercellular edema. The majority of the hair follicles are preserved but some show disruption or destruction of the wall by the inflammatory infiltrate. [20 ] Eosinophils are found within hair follicles in 95% of cases, in the sebaceous glands (65%), around sweat glands (80%), and in between collagen fibers (100%). The formation of abscesses in the follicles, sebaceous glands, or both is seen in 40% of cases. [6 ] In addition to eosinophils, there are variable numbers of neutrophils and some mononuclear cells. [21 ] Alcian blue stain reveals accumulation of acid mucopolysaccharides in spongiotic lesions of follicles or sebaceous glands (35%). Nissl modified staining reveals moderate increase in the number of tryptase-positive and chymase-negative mast cells surrounding follicles and sebaceous glands (100%). [6 ]

Because lesions of eosinophilic pustular folliculitis most often arise in seborrheic areas, some authors believe that a relationship exists between sebaceous gland activity and the development of papules and plaques. Fresh surface skin lipids from seborrheic areas in normal adults and lesional stratum corneum extracts from pustules of patients with EPF contain chemotactic substances for eosinophils and polymorphonuclear leukocytes (PMNs). [22 ] However, mechanisms that trigger the activation of follicular keratinocytes or the sebaceous glands to release cytokines, chemotactic factors, and intercellular adhesions molecule-1 are still poorly understood. Aside from eosinophils, the cells surrounding the sebaceous glands consist of T-helper lymphocytes, Langerhans' cells and macrophages. An increased number of mast cells has been described around hair follicles and sebaceous glands suggesting a role for these cells in the pathogenesis of the disease. [6 ] Within the sebaceous glands, markers of sebaceous gland differentiation (HMF 61, HMF 62, and OM-1) are markedly reduced while they were normally expressed in the hair follicles. Similarly, markers for acute inflammatory activation of the epithelia (ICAM-1 and MAC 387) were strongly expressed in the sebaceous glands while they were normal in the follicles. The relative propensity of the infiltrate towards the sebaceous glands rather than the hair follicles is clearly demonstrated in our case and has been observed by some authors. [5 ]

Various treatments have been tried for eosinophilic pustular folliculitis but no definite effective therapy has been established. Although systemic corticosteroids are the most commonly used first-line treatment, favorable effects have been observed with Indomethacin and Isotretinoin. The efficacy of oral or topical indomethacin may be secondary to the inhibition of cyclooxygenase, which in turn decreases the production of arachidonic acid-derived eosinophilic chemotactic factors, lipid chemotactic factor, 12-L-hydroxy-5,8,10-heptadecatrienoic acid, and prostaglandins.[6 ] On the other hand, Isotretinoin exerts anti-inflammatory action on PMNs, reduces chemotactic activity, and decreases the local synthesis of arachidonic acid-derived eosinophilic cationic factor. This is recommended as first-line treatment when histology shows primary involvement of the seboglandular units.[5 ]

The patient presented here was treated with oral Prednisone at 0.75 mg/kg/day on tapering doses for 8 weeks. There was noted immediate clearing of facial lesions upon initiation of treatment. The patient is now being given oral Indomethacin at 50 mg/day to control flares and remissions.

Summary

Background: Ofuji's disease or the "classic" eosinophilic pustular folliculitis is a rare dermatosis characterized by intermittent outbreaks of plaques with pustules mainly located in seborrheic areas. The histologic features show accumulation of eosinophils, neutrophils and lymphocytes around the pilosebaceous unit with some degree of spongiosis, and destruction of follicles.

Objectives: To demonstrate the clinical and histopathologic characteristics of a classic case of Ofuji's disease.

Patients/Methods: Examination revealed well-circumscribed erythematous, edematous plaques with overlying pustules and central clearing over the nose and malar area and histopathologic findings of a moderately dense perivascular and periadnexal inflammatory infiltration consisting of lymphocytes, numerous eosinophils, and some neutrophils. The sebaceous lobules and ducts are primarily affected with formation of eosinophilic abscesses within glands. Systemic corticosteroids are considered the treatment of choice in severe flares and are usually given in short courses. Indomethacin and Isotretinoin are excellent alternative treatments.

Conclusion: Recognition of the clinical and histopathologic presentation of a classic case of Ofuji's disease is important for immediate diagnosis and successful treatment despite its clinical course of flares and remissions.

References
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(Source: Dermatopathology: Practical & Conceptual July - September 2008 Volume 14, #3)