Letters to the Editor
4 Yokobayashi H, Sugaya M, Miyagaki T, Kai H, Minatani Y, Tamaki T. Serum chemokine levels in a case of angio-oedema associated with eosinophilia. Br J Dermatol 2008; 159: 738–740. 5 Motegi S, Hattori M, Tago O, Nagai Y, Ishikawa O. Elevated serum levels of TARC/CCL17, eotaxin-3/CCL26 and vascular endothelial
growth factor in a patient with non-episodic angioedema associated with eosinophilia and granulomatous cutaneous reaction. Eur J Dermatol 2013; 23: 524–526.
Refractory eosinophilic pustular folliculitis resistant to oral indomethacin successfully treated with adjuvant topical indomethacin Dear Editor, Eosinophilic pustular folliculitis (EPF) is characterized by pruritic, sterile follicular papulopustules, which often develop in seborrheic areas, primarily on the face. We report a case of a 48-year-old man with EPF, with skin lesions resistant to oral indomethacin (ID) alone, but responsive to combination treatment with topical ID. The patient developed an itchy rash on his cheeks 3 months earlier. Initially, symptoms subsided with topical and oral steroid treatment at a local clinic. The patient was referred to us when the rash recurred and spread with cessation of oral steroid. Physical examination revealed infiltrated erythema on the cheeks, nose, chest and upper back (Fig. 1a). Follicular pustulopapules were observed in the erythematous area. Skin biopsy of the cheek showed mixed infiltration of eosinophils and lymphocytes in and around hair follicles and sebaceous glands (Fig. 1b). Subsequently, EPF was diagnosed. Peripheral blood tests revealed a white blood cell count of 7980 cells/lL with 9.1% eosinophils. Serum level of thymus and activation regulated chemokine (TARC) was 1259 pg/mL but HIV antibodies were negative. The patient received 200 mg/day of oral indomethacin farnesyl (IF) for 2 weeks without any improvement. Treatment with 50 mg/day of diaphenylsulfone was also ineffective. The skin lesion showed transient improvement when the IF dose was increased to 400 mg/day, but recurred after 3 weeks with plaque formation (Fig. 1c). Treatment with 20 mg/day oral prednisolone combined with IF temporarily improved the skin lesion with the tendency of central clearing and residual pigmentation, but the eruption relapsed immediately after IF was discontinued. Topical application of tacrolimus did not show any favorable response. However, infiltrated erythema and papulopustules almost disappeared in 2 months only with topical ID treatment. When the facial erythema recurred, oral IF was reinstituted in combination with topical ID and the rash disappeared completely, together with normalization of eosinophil and TARC levels (Fig. 1d). Serum cytokine levels were measured in the course of treatment. Levels of eotaxin-3 were high in the early phase and lowered slowly after the skin lesion subsided. Levels of interleukin (IL)-4, IL-5 and IL-8 were also found to be elevated when
(a)
(b)
(c)
(d)
Figure 1. (a) Infiltrated erythema on the cheeks and nose at the first visit. (b) Mixed infiltration of eosinophils and lymphocytes in and around hair follicles and sebaceous glands (hematoxylin– eosin, original magnification 9200). (c) Aggravation of skin lesion during the treatment with oral indomethacin. (d) Improvement of skin lesion after the treatment with topical indomethacin. the skin lesion worsened. These results, together with the elevated level of TARC, indicate an aberrant T-helper (Th)2-type immune response underlies the pathogenesis of EPF as suggested previously.1,2 Although oral ID, an inhibitor of cyclooxygenase that produces prostaglandins, is effective in most cases of EPF, there are resistant cases with repeated recurrence. Topical steroids and tacrolimus were effective in some cases of EPF, but topical ID was less effective.3 Recently, it has been reported that hematopoietic prostaglandin D synthase is highly expressed in eosinophils in EPF lesions and eotaxin-3 (CCL26), a chemoattractant for eosinophils, is produced by sebocytes in lesional skin of EPF upon prostaglandin D2 stimulation in a peroxisome proliferator-activated receptor-c-dependent fashion.4 It is unlikely that the topical ID directly downregulated CRTH2.5 Nevertheless, our case suggests that topical ID, combined with oral
Correspondence: Wataru Fujimoto, M.D., Department of Dermatology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. Email: [email protected]
860
© 2014 Japanese Dermatological Association
Letters to the Editor
ID, synergistically suppress the pathogenic cascades of EPF in lesional skin, probably through its direct action on sebocytes, eosinophils and/or infiltrated Th2 cells.
CONFLICT OF INTEREST:
None declared.
Daigo OKA, Hiroaki HAYASHI, Wataru FUJIMOTO Department of Dermatology, Kawasaki Medical School, Kurashiki, Japan
2
3
4
doi: 10.1111/1346-8138.12595 5
REFERENCES
mRNA expression of interleukin 5 in peripheral blood mononuclear cells. Br J Dermatol 1996; 134: 766–772. Murayama T, Nakamura K, Tsuchida T. Eosinophilic pustular folliculitis with extensive distribution: correlation of serum TARC levels and peripheral blood eosinophil numbers. Int J Dermatol Published online: 2 April 2014; doi: 10.1111/ijd.12281 Katoh M, Nomura T, Miyachi Y, Kabashima K. Eosinophilic pustular folliculitis: a review of the Japanese published works. J Dermatol 2013; 40: 15–20. Nakahigashi K, Doi H, Otsuka A et al. PGD2 induces eotaxin-3 via PPARc from sebocytes: a possible pathogenesis of eosinophilic pustular folliculitis. J Allergy Clin Immunol 2012; 129: 536–543. Sato T, Shimura C, Miyagishi C, Yokozeki H. Indomethacin-induced reduction in CRTH2 in eosinophilic pustular folliculitis (Ofuji’s Disease): a proposed mechanism of action. Acta Derm Venereol 2010; 90: 18–22.
1 Fushimi M, Tokura Y, Sachi Y et al. Eosinophilic pustular folliculitis effectively treated with recombinant interferon-c: suppression of
Subcutaneous Sweet’s syndrome and neutrophilic panniculitis Dear Editor, The concepts of subcutaneous Sweet’s syndrome (SS) and neutrophilic panniculitis (NP) are similar, leading to confusion in the diagnosis of lesion(s) characterized by neutrophilic infiltration mainly in the subcutaneous tissue that are associated with a systemic disorder. Subcutaneous SS is regarded as a subtype of SS and is characterized by plaques or nodules with neutrophilic infiltration in either the subcutaneous tissue only, or in both the dermis and subcutis. In subcutaneous SS, the infiltration is found in either the lobules or the septa, or both, in addition to typical clinical findings of SS.1–3 NP is regarded as a distinctive clinical disorder characterized by plaques or nodules with neutrophilic infiltration of the lobules in subcutaneous tissue that is associated with myelodysplasia.4,5 Some researchers regard NP as a clinical entity that is distinct from SS,4,5 while others regard NP as a condition with a specific histopathological pattern that is not a distinct clinical entity.1 These differing opinions can be attributable to the fact that cases of neutrophilic infiltration in the subcutaneous tissue only do not fulfill the criteria for SS because of the absence of dermal infiltration (Table 1).2,3 If the criteria for SS are applied in a case of neutrophilic infiltration in the subcutaneous tissue only, the case is diagnosed as NP and not SS, supporting the opinion that NP is a distinct clinical entity. The diagnostic criteria of SS and NP are almost identical except for the main infiltration sites of dermis or subcutis, respectively (Tables 1,2),2–4 suggesting that SS and NP are two different conditions within the same disease spectrum. We propose that the term “NP” should be used only to describe the histopathological findings. We also propose that the criteria for SS should include “neutrophilic infiltration only in the
Table 1. Criteria of Sweet’s syndrome Two major criteria and more than two of four minor criteria have to be matched Major criteria (i) Abrupt onset of tender or painful erythematous plaques or nodules. (ii) Predominantly neutrophilic infiltration in the dermis without leukocytoclastic vasculitis. Minor criteria
(i) Preceded by a non-specific respiratory or gastrointestinal tract infection or vaccination or associated with: inflammatory diseases such as chronic autoimmune disorders, infections; hemoproliferative disorders or solid malignant tumors; and pregnancy. (ii) Accompanied by periods of general malaise and fever (>38°C) . (iii) Laboratory values during onset: erythrocyte sedimentation rate, >20 mm; C-reactive protein positive; segmented-nuclear neutrophils and stabs, >70% in peripheral blood smear; leukocytosis, >8000 (three of four of these values necessary). (iv) Excellent response to treatment with systemic corticosteroids or potassium iodide.
subcutaneous tissue”. Using our proposals, the concepts of subcutaneous SS and NP will be clearer, and cases with neutrophilic infiltration mainly in the subcutaneous tissue can be
Correspondence: Yoshimasa Nobeyama, M.D., Ph.D., Department of Dermatology, The Jikei University School of Medicine, 25-8 Nishi-shimbashi 3-chome, Minato-ku, Tokyo 105-8461, Japan. Email: [email protected]
© 2014 Japanese Dermatological Association
861
4 Yokobayashi H, Sugaya M, Miyagaki T, Kai H, Minatani Y, Tamaki T. Serum chemokine levels in a case of angio-oedema associated with eosinophilia. Br J Dermatol 2008; 159: 738–740. 5 Motegi S, Hattori M, Tago O, Nagai Y, Ishikawa O. Elevated serum levels of TARC/CCL17, eotaxin-3/CCL26 and vascular endothelial
growth factor in a patient with non-episodic angioedema associated with eosinophilia and granulomatous cutaneous reaction. Eur J Dermatol 2013; 23: 524–526.
Refractory eosinophilic pustular folliculitis resistant to oral indomethacin successfully treated with adjuvant topical indomethacin Dear Editor, Eosinophilic pustular folliculitis (EPF) is characterized by pruritic, sterile follicular papulopustules, which often develop in seborrheic areas, primarily on the face. We report a case of a 48-year-old man with EPF, with skin lesions resistant to oral indomethacin (ID) alone, but responsive to combination treatment with topical ID. The patient developed an itchy rash on his cheeks 3 months earlier. Initially, symptoms subsided with topical and oral steroid treatment at a local clinic. The patient was referred to us when the rash recurred and spread with cessation of oral steroid. Physical examination revealed infiltrated erythema on the cheeks, nose, chest and upper back (Fig. 1a). Follicular pustulopapules were observed in the erythematous area. Skin biopsy of the cheek showed mixed infiltration of eosinophils and lymphocytes in and around hair follicles and sebaceous glands (Fig. 1b). Subsequently, EPF was diagnosed. Peripheral blood tests revealed a white blood cell count of 7980 cells/lL with 9.1% eosinophils. Serum level of thymus and activation regulated chemokine (TARC) was 1259 pg/mL but HIV antibodies were negative. The patient received 200 mg/day of oral indomethacin farnesyl (IF) for 2 weeks without any improvement. Treatment with 50 mg/day of diaphenylsulfone was also ineffective. The skin lesion showed transient improvement when the IF dose was increased to 400 mg/day, but recurred after 3 weeks with plaque formation (Fig. 1c). Treatment with 20 mg/day oral prednisolone combined with IF temporarily improved the skin lesion with the tendency of central clearing and residual pigmentation, but the eruption relapsed immediately after IF was discontinued. Topical application of tacrolimus did not show any favorable response. However, infiltrated erythema and papulopustules almost disappeared in 2 months only with topical ID treatment. When the facial erythema recurred, oral IF was reinstituted in combination with topical ID and the rash disappeared completely, together with normalization of eosinophil and TARC levels (Fig. 1d). Serum cytokine levels were measured in the course of treatment. Levels of eotaxin-3 were high in the early phase and lowered slowly after the skin lesion subsided. Levels of interleukin (IL)-4, IL-5 and IL-8 were also found to be elevated when
(a)
(b)
(c)
(d)
Figure 1. (a) Infiltrated erythema on the cheeks and nose at the first visit. (b) Mixed infiltration of eosinophils and lymphocytes in and around hair follicles and sebaceous glands (hematoxylin– eosin, original magnification 9200). (c) Aggravation of skin lesion during the treatment with oral indomethacin. (d) Improvement of skin lesion after the treatment with topical indomethacin. the skin lesion worsened. These results, together with the elevated level of TARC, indicate an aberrant T-helper (Th)2-type immune response underlies the pathogenesis of EPF as suggested previously.1,2 Although oral ID, an inhibitor of cyclooxygenase that produces prostaglandins, is effective in most cases of EPF, there are resistant cases with repeated recurrence. Topical steroids and tacrolimus were effective in some cases of EPF, but topical ID was less effective.3 Recently, it has been reported that hematopoietic prostaglandin D synthase is highly expressed in eosinophils in EPF lesions and eotaxin-3 (CCL26), a chemoattractant for eosinophils, is produced by sebocytes in lesional skin of EPF upon prostaglandin D2 stimulation in a peroxisome proliferator-activated receptor-c-dependent fashion.4 It is unlikely that the topical ID directly downregulated CRTH2.5 Nevertheless, our case suggests that topical ID, combined with oral
Correspondence: Wataru Fujimoto, M.D., Department of Dermatology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. Email: [email protected]
860
© 2014 Japanese Dermatological Association
Letters to the Editor
ID, synergistically suppress the pathogenic cascades of EPF in lesional skin, probably through its direct action on sebocytes, eosinophils and/or infiltrated Th2 cells.
CONFLICT OF INTEREST:
None declared.
Daigo OKA, Hiroaki HAYASHI, Wataru FUJIMOTO Department of Dermatology, Kawasaki Medical School, Kurashiki, Japan
2
3
4
doi: 10.1111/1346-8138.12595 5
REFERENCES
mRNA expression of interleukin 5 in peripheral blood mononuclear cells. Br J Dermatol 1996; 134: 766–772. Murayama T, Nakamura K, Tsuchida T. Eosinophilic pustular folliculitis with extensive distribution: correlation of serum TARC levels and peripheral blood eosinophil numbers. Int J Dermatol Published online: 2 April 2014; doi: 10.1111/ijd.12281 Katoh M, Nomura T, Miyachi Y, Kabashima K. Eosinophilic pustular folliculitis: a review of the Japanese published works. J Dermatol 2013; 40: 15–20. Nakahigashi K, Doi H, Otsuka A et al. PGD2 induces eotaxin-3 via PPARc from sebocytes: a possible pathogenesis of eosinophilic pustular folliculitis. J Allergy Clin Immunol 2012; 129: 536–543. Sato T, Shimura C, Miyagishi C, Yokozeki H. Indomethacin-induced reduction in CRTH2 in eosinophilic pustular folliculitis (Ofuji’s Disease): a proposed mechanism of action. Acta Derm Venereol 2010; 90: 18–22.
1 Fushimi M, Tokura Y, Sachi Y et al. Eosinophilic pustular folliculitis effectively treated with recombinant interferon-c: suppression of
Subcutaneous Sweet’s syndrome and neutrophilic panniculitis Dear Editor, The concepts of subcutaneous Sweet’s syndrome (SS) and neutrophilic panniculitis (NP) are similar, leading to confusion in the diagnosis of lesion(s) characterized by neutrophilic infiltration mainly in the subcutaneous tissue that are associated with a systemic disorder. Subcutaneous SS is regarded as a subtype of SS and is characterized by plaques or nodules with neutrophilic infiltration in either the subcutaneous tissue only, or in both the dermis and subcutis. In subcutaneous SS, the infiltration is found in either the lobules or the septa, or both, in addition to typical clinical findings of SS.1–3 NP is regarded as a distinctive clinical disorder characterized by plaques or nodules with neutrophilic infiltration of the lobules in subcutaneous tissue that is associated with myelodysplasia.4,5 Some researchers regard NP as a clinical entity that is distinct from SS,4,5 while others regard NP as a condition with a specific histopathological pattern that is not a distinct clinical entity.1 These differing opinions can be attributable to the fact that cases of neutrophilic infiltration in the subcutaneous tissue only do not fulfill the criteria for SS because of the absence of dermal infiltration (Table 1).2,3 If the criteria for SS are applied in a case of neutrophilic infiltration in the subcutaneous tissue only, the case is diagnosed as NP and not SS, supporting the opinion that NP is a distinct clinical entity. The diagnostic criteria of SS and NP are almost identical except for the main infiltration sites of dermis or subcutis, respectively (Tables 1,2),2–4 suggesting that SS and NP are two different conditions within the same disease spectrum. We propose that the term “NP” should be used only to describe the histopathological findings. We also propose that the criteria for SS should include “neutrophilic infiltration only in the
Table 1. Criteria of Sweet’s syndrome Two major criteria and more than two of four minor criteria have to be matched Major criteria (i) Abrupt onset of tender or painful erythematous plaques or nodules. (ii) Predominantly neutrophilic infiltration in the dermis without leukocytoclastic vasculitis. Minor criteria
(i) Preceded by a non-specific respiratory or gastrointestinal tract infection or vaccination or associated with: inflammatory diseases such as chronic autoimmune disorders, infections; hemoproliferative disorders or solid malignant tumors; and pregnancy. (ii) Accompanied by periods of general malaise and fever (>38°C) . (iii) Laboratory values during onset: erythrocyte sedimentation rate, >20 mm; C-reactive protein positive; segmented-nuclear neutrophils and stabs, >70% in peripheral blood smear; leukocytosis, >8000 (three of four of these values necessary). (iv) Excellent response to treatment with systemic corticosteroids or potassium iodide.
subcutaneous tissue”. Using our proposals, the concepts of subcutaneous SS and NP will be clearer, and cases with neutrophilic infiltration mainly in the subcutaneous tissue can be
Correspondence: Yoshimasa Nobeyama, M.D., Ph.D., Department of Dermatology, The Jikei University School of Medicine, 25-8 Nishi-shimbashi 3-chome, Minato-ku, Tokyo 105-8461, Japan. Email: [email protected]
© 2014 Japanese Dermatological Association
861
