Case report
Eosinophilic pustular folliculitis with extensive distribution: correlation of serum TARC levels and peripheral blood eosinophil numbers Takayuki Murayama, MD, Koichiro Nakamura, MD, and Tetsuya Tsuchida, MD
Department of Dermatology, Saitama Medical University, Saitama, Japan Correspondence Koichiro Nakamura, MD Department of Dermatology Saitama Medical University 38 Morohogo Moroyama-machi Iruma-gum Saitama 350-0495 Japan E-mail: [email protected] Conflicts of interest: None.
Eosinophilic pustular folliculitis (EPF) was first described by Ofuji in 1970.1 We report a case of EPF with extensive eruption, with manifestations on the face, extremities, palms, soles, and trunk. Case report A 62-year-old man noted an itchy eruption on his palms and soles, which gradually expanded to the face, extremities, and trunk, during May 2009. He presented at our hospital in July 2009. The eruption was apparent on the patient’s scalp, face, trunk, extremities, and palms and soles (Fig. 1). Clinical examination revealed slightly increased levels of peripheral blood eosinophils. The patient’s serological human immunodeficiency virus (HIV) titer was negative. Histological examination of the pustular follicular erythema on the subject’s face showed numerous eosinophils infiltrating the hair follicles and the destruction of hair walls (Fig. 2). The numerous eosinophils also infiltrated the sebaceous gland. Histological examination of the erythematous macules with pustules on the patient’s lower leg showed intraepidermal pustules with neutrophil and eosinophil infiltration. Eosinophilic pustular folliculitis was diagnosed according to clinical and histological findings. The patient was treated with oral indomethacin and minocycline. However, the minocycline ª 2014 The International Society of Dermatology
was ineffective and, because of the occurrence of itchiness, indomethacin was stopped for two weeks (Fig. 3). The subject was treated with oral prednisolone at 15 mg/d along with topical corticosteroid ointment (difluprednate ointment and clobetasol ointment) from September 2009. The erythematous macules gradually improved and oral prednisolone was gradually decreased and withdrawn in May 2011 after two years of treatment. Peripheral blood eosinophil numbers showed maximum levels and then gradually decreased to within normal ranges. Serum TARC (thymus and activation-regulated chemokine, CCL17) levels were also examined. Serum TARC reached a maximum level in October 2009 and then gradually decreased in parallel with peripheral blood eosinophils. Discussion The present case was considered to represent EPF with extensive eruption, with manifestations on the face, extremities, palms, soles, and trunk. Widespread eruption as in the present patient has been reported to be rare.2 Eosinophilic pustular folliculitis has recently been classified in three subtypes, including the classical type, immunodeficiency type, and infantile type.3,4 Classical EPF occurs more often in male patients and is often detected in Asian populations. In classical EPF, erythematous International Journal of Dermatology 2015, 54, 1071–1074
1071
1072
Case report
Eosinophilic pustular folliculitis with extensive distribution
Murayama, Nakamura and Tsuchida
(a)
(b)
(c)
(d)
(e)
(f)
(g)
Figure 1 Clinical examination in a 62-year-old man shows pustular lesions in erythematous plaque on the (a) face, (b) trunk, (c) palm, (d) hand, (e, f) lower extremity (including pustular formations) and (g) foot
plaque is detected on the face and trunk. In immunosuppressive EPF, papular and urticarial lesions are often detected on the face, scalp, neck, and other sites. Other recently identified causes of EPF include medication, transplantation, pregnancy, and various diseases.5–8 The present case was considered to represent classical EPF, in which extensive eruptions are reported to be rare.2,3 Secondly, we clarified the involvement of TARC in the pathogenesis of EPF. Eotaxin-1, interleukin 5 (IL-5), and IL-13 are known to play roles in the recruitment of eosinophils and Th2 cells in EPF lesions.9 The present patient showed high serum TARC levels that mirrored the course International Journal of Dermatology 2015, 54, 1071–1074
of eruption. TARC is a chemokine that attracts and activates Th2 cells and also contributes to the recruitment of eosinophils. We have previously indicated that serum TARC levels reflect disease activity in atopic dermatitis, as well as in bullous pemphigoid, the lesions of which are infiltrated by eosinophils and Th2 cells.10,11 In the present patient, serum TARC was closely associated with peripheral blood eosinophil numbers as well as with clinical improvement. As far as we know, this is the first report to indicate that EPF shows increased levels of serum TARC. Thus, we suggest that serum TARC levels may be associated with the clinical severity of EPF. Because serum ª 2014 The International Society of Dermatology
Murayama, Nakamura and Tsuchida
Eosinophilic pustular folliculitis with extensive distribution
(a)
Case report
(b)
(c)
Figure 2 Histopathology of a biopsy from the pustular erythema on the face. (a) Massive eosinophilic infiltration is detected in the hair follicle space. (b) Prominent eosinophilic infiltration is detected inside the hair follicle and outside the lesion around the hair follicle. (c) Prominent eosinophilic infiltration is detected inside the sebaceous gland. [Hematoxylin and eosin stain; original magnification (a–c) 940.]
Dexathamethasone propionate acid ointment
Indomethacin
Prednisolone 15 mg/day 10 mg/day
5 mg/day
Minocycline IPD Eruption
2009 7
2010 1
2011 1
4000
1000
2000
500
(year) (month)
Figure 3 Clinical course and treatment, showing changes in peripheral ○: Blood eosinophils (/lL) and ●: Serum TARC (pg/mL) during treatment. The patient was treated with indomethacin, followed by oral prednisolone. Increased peripheral blood eosinophil numbers and high serum TARC levels were detected at the start of treatment; these gradually declined as treatment progressed. Suplatast tosilate (300 mg/day)
TARC levels in patients with psoriasis are within the normal range, establishing serum TARC levels may be useful in the diagnosis of EPF. Because other chemokines such as ª 2014 The International Society of Dermatology
eptaxin-1 and IL-5 are important in the recruitment of eosinophils, further analysis of these chemokines in addition to TARC would clarify the pathogenesis of EPF. International Journal of Dermatology 2015, 54, 1071–1074
1073
1074
Case report
Eosinophilic pustular folliculitis with extensive distribution
Thirdly, the present patient showed palmoplantar eruption along with eruptions over the entire body. Aoyama and Tagami reported palmoplantar eruption in 18% of 207 EPF patients.12 The palmoplantar eruption occurred an average of 26 months prior to the appearance of disease at other sites. Patients in whom the first signs of disease appeared on the palms and soles tended to be male and showed slightly higher levels of eosinophils. Thus, these data indicate that when a prolonged palmoplantar pustule formation is being investigated, EPF should be considered in the differential diagnosis, especially when the initial onset of palmoplantar pustule formation proceeds to involve the whole body, as in the present patient. We have reported a rare manifestation of EPF. The present case will serve to stimulate speculation on how TARC may be associated with the pathogenesis of EPF. References 1 Ofuji S, Ogino A, Horio T, et al. Eosinophilic pustular folliculitis. Acta Derm Venereol 1970; 50: 195–203. 2 Ishiguro N, Shishido E, Okamoto R, et al. Ofujis disease: a report on 20 patients with clinical and histopathologic analysis. J Am Acad Dermatol 2003; 46: 827–833. 3 Nervi SJ, Schwartz RA, Dmochowski M, et al. Eosinophilic pustular folliculitis: a 40-year retrospect. J Am Acad Dermatol 2006; 55: 285–289. 4 Razera F, Olm GS, Bonamigo RR. Neutrophilic dermatosis – part II. An Bras Dermatol 2011; 86: 195–211.
International Journal of Dermatology 2015, 54, 1071–1074
Murayama, Nakamura and Tsuchida
5 Keida T, Hayashi N, Kawashima M. Eosinophilic pustular folliculitis following autologous peripheral blood stem cell transplantation. J Dermatol 2004; 31: 21–26. 6 Maejima H, Mukai H, Hikaru E. Eosinophilic pustular folliculitis induced by allopurinol and timepidium bromide. Acta Derm Venereol 2002; 82: 316–317. 7 Wong TW, Tsai YM, Lee JY. Eosinophilic pustular folliculitis (Ofuji’s disease) in a patient with silicone tissue augmentation. J Dermatol 2004; 31: 727–730. 8 Kimoto M, Ihihara S, Konohana A. Eosinophilic pustular folliculitis with polycythemia vera. Dermatology 2005; 210: 239–240. 9 Amerio P, Frezzolini A, Feliciani C, et al. Eotaxins and CCR3 receptor in inflammatory and allergic skin diseases: therapeutic implications. Curr Drug Targets Inflamm Allergy 2003; 2: 81–94. 10 Kakinuma T, Nakamura K, Wakugawa M, et al. Thymus and activation-regulated chemokine in atopic dermatitis: serum thymus and activation-regulated chemokine level is closely associated with disease activity. J Allergy Clin Immunol 2001; 107: 535–541. 11 Kakinuma T, Wakugawa M, Nakamura K, et al. High level of thymus and activation-regulated chemokine in blister fluid and sera of patients with bullous pemphigoid. Br J Dermatol 2003; 148: 203–210. 12 Aoyama H, Tagami H. Pustular folliculitis starting initially only with palmoplantar pustular lesions. Dermatology 1992; 185: 276–280.
ª 2014 The International Society of Dermatology
Eosinophilic pustular folliculitis with extensive distribution: correlation of serum TARC levels and peripheral blood eosinophil numbers Takayuki Murayama, MD, Koichiro Nakamura, MD, and Tetsuya Tsuchida, MD
Department of Dermatology, Saitama Medical University, Saitama, Japan Correspondence Koichiro Nakamura, MD Department of Dermatology Saitama Medical University 38 Morohogo Moroyama-machi Iruma-gum Saitama 350-0495 Japan E-mail: [email protected] Conflicts of interest: None.
Eosinophilic pustular folliculitis (EPF) was first described by Ofuji in 1970.1 We report a case of EPF with extensive eruption, with manifestations on the face, extremities, palms, soles, and trunk. Case report A 62-year-old man noted an itchy eruption on his palms and soles, which gradually expanded to the face, extremities, and trunk, during May 2009. He presented at our hospital in July 2009. The eruption was apparent on the patient’s scalp, face, trunk, extremities, and palms and soles (Fig. 1). Clinical examination revealed slightly increased levels of peripheral blood eosinophils. The patient’s serological human immunodeficiency virus (HIV) titer was negative. Histological examination of the pustular follicular erythema on the subject’s face showed numerous eosinophils infiltrating the hair follicles and the destruction of hair walls (Fig. 2). The numerous eosinophils also infiltrated the sebaceous gland. Histological examination of the erythematous macules with pustules on the patient’s lower leg showed intraepidermal pustules with neutrophil and eosinophil infiltration. Eosinophilic pustular folliculitis was diagnosed according to clinical and histological findings. The patient was treated with oral indomethacin and minocycline. However, the minocycline ª 2014 The International Society of Dermatology
was ineffective and, because of the occurrence of itchiness, indomethacin was stopped for two weeks (Fig. 3). The subject was treated with oral prednisolone at 15 mg/d along with topical corticosteroid ointment (difluprednate ointment and clobetasol ointment) from September 2009. The erythematous macules gradually improved and oral prednisolone was gradually decreased and withdrawn in May 2011 after two years of treatment. Peripheral blood eosinophil numbers showed maximum levels and then gradually decreased to within normal ranges. Serum TARC (thymus and activation-regulated chemokine, CCL17) levels were also examined. Serum TARC reached a maximum level in October 2009 and then gradually decreased in parallel with peripheral blood eosinophils. Discussion The present case was considered to represent EPF with extensive eruption, with manifestations on the face, extremities, palms, soles, and trunk. Widespread eruption as in the present patient has been reported to be rare.2 Eosinophilic pustular folliculitis has recently been classified in three subtypes, including the classical type, immunodeficiency type, and infantile type.3,4 Classical EPF occurs more often in male patients and is often detected in Asian populations. In classical EPF, erythematous International Journal of Dermatology 2015, 54, 1071–1074
1071
1072
Case report
Eosinophilic pustular folliculitis with extensive distribution
Murayama, Nakamura and Tsuchida
(a)
(b)
(c)
(d)
(e)
(f)
(g)
Figure 1 Clinical examination in a 62-year-old man shows pustular lesions in erythematous plaque on the (a) face, (b) trunk, (c) palm, (d) hand, (e, f) lower extremity (including pustular formations) and (g) foot
plaque is detected on the face and trunk. In immunosuppressive EPF, papular and urticarial lesions are often detected on the face, scalp, neck, and other sites. Other recently identified causes of EPF include medication, transplantation, pregnancy, and various diseases.5–8 The present case was considered to represent classical EPF, in which extensive eruptions are reported to be rare.2,3 Secondly, we clarified the involvement of TARC in the pathogenesis of EPF. Eotaxin-1, interleukin 5 (IL-5), and IL-13 are known to play roles in the recruitment of eosinophils and Th2 cells in EPF lesions.9 The present patient showed high serum TARC levels that mirrored the course International Journal of Dermatology 2015, 54, 1071–1074
of eruption. TARC is a chemokine that attracts and activates Th2 cells and also contributes to the recruitment of eosinophils. We have previously indicated that serum TARC levels reflect disease activity in atopic dermatitis, as well as in bullous pemphigoid, the lesions of which are infiltrated by eosinophils and Th2 cells.10,11 In the present patient, serum TARC was closely associated with peripheral blood eosinophil numbers as well as with clinical improvement. As far as we know, this is the first report to indicate that EPF shows increased levels of serum TARC. Thus, we suggest that serum TARC levels may be associated with the clinical severity of EPF. Because serum ª 2014 The International Society of Dermatology
Murayama, Nakamura and Tsuchida
Eosinophilic pustular folliculitis with extensive distribution
(a)
Case report
(b)
(c)
Figure 2 Histopathology of a biopsy from the pustular erythema on the face. (a) Massive eosinophilic infiltration is detected in the hair follicle space. (b) Prominent eosinophilic infiltration is detected inside the hair follicle and outside the lesion around the hair follicle. (c) Prominent eosinophilic infiltration is detected inside the sebaceous gland. [Hematoxylin and eosin stain; original magnification (a–c) 940.]
Dexathamethasone propionate acid ointment
Indomethacin
Prednisolone 15 mg/day 10 mg/day
5 mg/day
Minocycline IPD Eruption
2009 7
2010 1
2011 1
4000
1000
2000
500
(year) (month)
Figure 3 Clinical course and treatment, showing changes in peripheral ○: Blood eosinophils (/lL) and ●: Serum TARC (pg/mL) during treatment. The patient was treated with indomethacin, followed by oral prednisolone. Increased peripheral blood eosinophil numbers and high serum TARC levels were detected at the start of treatment; these gradually declined as treatment progressed. Suplatast tosilate (300 mg/day)
TARC levels in patients with psoriasis are within the normal range, establishing serum TARC levels may be useful in the diagnosis of EPF. Because other chemokines such as ª 2014 The International Society of Dermatology
eptaxin-1 and IL-5 are important in the recruitment of eosinophils, further analysis of these chemokines in addition to TARC would clarify the pathogenesis of EPF. International Journal of Dermatology 2015, 54, 1071–1074
1073
1074
Case report
Eosinophilic pustular folliculitis with extensive distribution
Thirdly, the present patient showed palmoplantar eruption along with eruptions over the entire body. Aoyama and Tagami reported palmoplantar eruption in 18% of 207 EPF patients.12 The palmoplantar eruption occurred an average of 26 months prior to the appearance of disease at other sites. Patients in whom the first signs of disease appeared on the palms and soles tended to be male and showed slightly higher levels of eosinophils. Thus, these data indicate that when a prolonged palmoplantar pustule formation is being investigated, EPF should be considered in the differential diagnosis, especially when the initial onset of palmoplantar pustule formation proceeds to involve the whole body, as in the present patient. We have reported a rare manifestation of EPF. The present case will serve to stimulate speculation on how TARC may be associated with the pathogenesis of EPF. References 1 Ofuji S, Ogino A, Horio T, et al. Eosinophilic pustular folliculitis. Acta Derm Venereol 1970; 50: 195–203. 2 Ishiguro N, Shishido E, Okamoto R, et al. Ofujis disease: a report on 20 patients with clinical and histopathologic analysis. J Am Acad Dermatol 2003; 46: 827–833. 3 Nervi SJ, Schwartz RA, Dmochowski M, et al. Eosinophilic pustular folliculitis: a 40-year retrospect. J Am Acad Dermatol 2006; 55: 285–289. 4 Razera F, Olm GS, Bonamigo RR. Neutrophilic dermatosis – part II. An Bras Dermatol 2011; 86: 195–211.
International Journal of Dermatology 2015, 54, 1071–1074
Murayama, Nakamura and Tsuchida
5 Keida T, Hayashi N, Kawashima M. Eosinophilic pustular folliculitis following autologous peripheral blood stem cell transplantation. J Dermatol 2004; 31: 21–26. 6 Maejima H, Mukai H, Hikaru E. Eosinophilic pustular folliculitis induced by allopurinol and timepidium bromide. Acta Derm Venereol 2002; 82: 316–317. 7 Wong TW, Tsai YM, Lee JY. Eosinophilic pustular folliculitis (Ofuji’s disease) in a patient with silicone tissue augmentation. J Dermatol 2004; 31: 727–730. 8 Kimoto M, Ihihara S, Konohana A. Eosinophilic pustular folliculitis with polycythemia vera. Dermatology 2005; 210: 239–240. 9 Amerio P, Frezzolini A, Feliciani C, et al. Eotaxins and CCR3 receptor in inflammatory and allergic skin diseases: therapeutic implications. Curr Drug Targets Inflamm Allergy 2003; 2: 81–94. 10 Kakinuma T, Nakamura K, Wakugawa M, et al. Thymus and activation-regulated chemokine in atopic dermatitis: serum thymus and activation-regulated chemokine level is closely associated with disease activity. J Allergy Clin Immunol 2001; 107: 535–541. 11 Kakinuma T, Wakugawa M, Nakamura K, et al. High level of thymus and activation-regulated chemokine in blister fluid and sera of patients with bullous pemphigoid. Br J Dermatol 2003; 148: 203–210. 12 Aoyama H, Tagami H. Pustular folliculitis starting initially only with palmoplantar pustular lesions. Dermatology 1992; 185: 276–280.
ª 2014 The International Society of Dermatology
