Letters to the Editor
Acute generalized exanthematous pustulosis induced by oral prednisolone Dear Editor, Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption commonly induced by drugs such as antibiotics. AGEP is characterized by rapidly spreading, nonfollicular and small pustular eruptions in combination with fever and leukocytosis, especially neutrophilia.1 The prognosis is not usually severe, but AGEP may be fatal in a subset of cases (1–2%), especially in elderly patients.1 Thus, immediate diagnosis and prompt discontinuation of the causative drug are important. We here report on a 46-year-old woman with a 12-year history of primary biliary cirrhosis. Her liver dysfunction worsened and a liver biopsy was performed. She was histopathologically diagnosed with overlap syndrome of primary biliary cirrhosis and autoimmune hepatitis, and was given systemic 10 mg prednisolone and 10 mg rabeprazole sodium. The next day after the initiation of this therapy, she developed erythema on the chest and axillae. Because drug eruption was suspected, rabeprazole sodium was stopped. However, pustules, scattered red papules and scarlet color edematous erythema were noted on her whole body (Fig. 1a,b). A skin biopsy specimen taken from the pustules demonstrated neutrophilic pustules under the stratum corneum and lymphocytic, eosinophilic and neutrophilic infiltrates in the upper dermis (Fig. 1c). Laboratory examinations showed the following values: white blood cells, 6.83 9 103/lL; neutrophils, 4.03 9 103/lL; and eosinophils, 0.83 9 103/lL. Bacterial culture of the pustule was negative. Results of the druginduced lymphocyte stimulation test of prednisolone and rabeprazole sodium were negative. Consequently, she was diagnosed with AGEP. Systemic prednisolone was stopped 10 days after initiation and her rash disappeared 3 days later. Seventeen months later, her hepatitis worsened, and she required a liver transplantation and steroid administration. Results of a patch test performed with prednisolone 10%, betamethasone 10% and Vaseline (negative control) revealed a positive reaction to prednisolone after 24 and 72 h (Fig. 1d). Another patch test was performed with prednisolone sodium succinate, hydrocortisone, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, methylprednisolone, methylprednisolone sodium succinate, dexamethasone and dexamethasone sodium phosphate. In addition, a patch test was performed with medicinal substances of prednisolone, including lactose hydrate, corn starch and hydroxypropyl cellulose. Results of these patch tests were negative. We diagnosed this case as AGEP
(a)
(b)
(c)
(d)
Figure 1. (a) Clinical findings on the ventral side of the trunk. Red papules and scarlet colored edematous erythema are seen on the whole body. (b) Multiple pustules were observed on the erythematous plaques. (c) Histopathological examination revealed neutrophilic pustules under the stratum corneum, and lymphocytic, eosinophilic and neutrophilic infiltrates in the upper dermis (hematoxylin–eosin, original magnification 9400). (d) Patch test revealed a positive reaction to prednisolone after 24 h.
induced by prednisolone. Subsequently, methylprednisolone sodium succinate treatment was initiated for hepatitis, which was well tolerated. Corticosteroids, which are widely used because of their anti-inflammatory and immunosuppressive effects, have been reported to induce a variety of adverse drug reactions, including contact dermatitis. However, generalized hypersensitivity reactions after systemic administration of corticosteroids are rare.2 Reported cases of AGEP induced by corticosteroids are especially few. Although it has been reported that the sensitivity of patch testing to drugs in AGEP is approximately 50%,3,4 in this case, AGEP was successfully confirmed by patch test. The patient had never taken oral prednisolone, but had been treated with topical prednisolone ointment 10 years previously
Correspondence: Toshio Hasegawa, M.D., Ph.D., Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Email: [email protected]
© 2014 Japanese Dermatological Association
1135
Letters to the Editor
for acne. It is possible that she was previously sensitized to prednisolone by the ointment. We should be careful in using corticosteroids, because even prednisolone can cause drug eruption.
CONFLICT OF INTEREST:
None.
Satoko ISHII,1 Toshio HASEGAWA,1 Yusuke HIRASAWA,1 Yuichiro TSUNEMI,2 Makoto KAWASHIMA,2 Shigaku IKEDA1 1
Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, and 2Department of Dermatology, Tokyo Women’s Medical University, Tokyo, Japan
doi: 10.1111/1346-8138.12658
REFERENCES 1 Roujeau JC, Bioulac-Sage P, Bourseau C et al. Acute generalized exanthematic pustulosis: analysis of 63 cases. Arch Dermatol 1991; 127: 1333–1338. 2 Bircher AJ, Levy F, Langauer S, Lepoittevin JP. Contact allergy to topical corticosteroids and systemic contact dermatitis from prednisolone with tolerance of triamcinolone. Acta Derm Venereol 1995; 75: 490–493. 3 Demitsu T, Kosuge A, Yamada T. Acute generalized exanthematous pustulosis induced by dexamethasone injection. Dermatology 1996; 193: 56–58. 4 Mussot-Chia C, Flechet ML, Napolitano M et al. Methylprednisoloneinduced acute generalized exanthematous pustulosis. Ann Dermatol Venereol 2001; 128: 241–243.
Elevation of serum KL-6 levels during treatment with tumor necrosis factor-a inhibitor in patients with psoriasis Dear Editor, KL-6 is a serum biomarker for detection of various interstitial lung diseases.1 Herein, we investigated the correlation between biologic treatment and elevation of serum KL-6 levels in Japanese psoriatic patients. A total of 19 psoriatic patients whose serum KL-6 levels were measured before initiation of biologic therapy and followed up for at least 6 months were analyzed (Table 1). Serum KL-6 levels were measured using LUMIPULSEâ KL-6 Eisai or NANOPIAâ KL-6 Eisai (Eisia, Tokyo,
Japan) by in-house laboratory. Of these 19 patients, none showed an increase within the first year. In the patients who were followed up for more than a year, serum KL-6 levels exceeded the upper normal limit of 500 U/mL in three of seven patients treated with adalimumab. Mean serum KL-6 level at maximum during adalimumab therapy (376.9 268.6 U/mL) showed significant increase (P = 0.03, paired Student’s t-test). None had clinical symptoms or computed tomography scan findings of pneumonia. In contrast, elevation of serum KL-6
Table 1. Characteristics of the enrolled psoriatic patients Adalimumab‡ No. Sex Male (%) Female (%) Age at baseline† (years) Type of psoriasis Psoriasis vulgaris Psoriatic arthritis Generalized pustular psoriasis Follow-up period† (months) Serum KL-6 level at baseline† (U/mL) Serum KL-6 level at maximum† (U/mL) No. of patients whose serum KL-6 levels exceeded 500 U/mL Treatment history of methotrexate Past history of interstitial lung diseases
7
Infliximab 4
Ustekinumab§ 8
5 (71%) 2 (29%) 49.7 12.6
2 (50%) 2 (50%) 58.3 14.5
7 (88%) 1 (12%) 48.5 16.7
4 2 1 22.0 10.2 196.0 70.2 376.9 268.6 3
0 3 1 16.0 9.6 186.0 87.5 223.8 59.6 0
7 1 0 15.8 7.5 213.7 82.9 191.0 53.0 0
0 0
2¶ 0
0 0
† Mean standard deviation. ‡One case is a switcher from infliximab. §Two cases had history of previous infliximab treatment. ¶One case is treated with combination therapy. One case had history of previous treatment.
Correspondence: Tomotaka Mabuchi, M.D., Ph.D., Department of Dermatology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan. Email: [email protected]
1136
© 2014 Japanese Dermatological Association
Acute generalized exanthematous pustulosis induced by oral prednisolone Dear Editor, Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption commonly induced by drugs such as antibiotics. AGEP is characterized by rapidly spreading, nonfollicular and small pustular eruptions in combination with fever and leukocytosis, especially neutrophilia.1 The prognosis is not usually severe, but AGEP may be fatal in a subset of cases (1–2%), especially in elderly patients.1 Thus, immediate diagnosis and prompt discontinuation of the causative drug are important. We here report on a 46-year-old woman with a 12-year history of primary biliary cirrhosis. Her liver dysfunction worsened and a liver biopsy was performed. She was histopathologically diagnosed with overlap syndrome of primary biliary cirrhosis and autoimmune hepatitis, and was given systemic 10 mg prednisolone and 10 mg rabeprazole sodium. The next day after the initiation of this therapy, she developed erythema on the chest and axillae. Because drug eruption was suspected, rabeprazole sodium was stopped. However, pustules, scattered red papules and scarlet color edematous erythema were noted on her whole body (Fig. 1a,b). A skin biopsy specimen taken from the pustules demonstrated neutrophilic pustules under the stratum corneum and lymphocytic, eosinophilic and neutrophilic infiltrates in the upper dermis (Fig. 1c). Laboratory examinations showed the following values: white blood cells, 6.83 9 103/lL; neutrophils, 4.03 9 103/lL; and eosinophils, 0.83 9 103/lL. Bacterial culture of the pustule was negative. Results of the druginduced lymphocyte stimulation test of prednisolone and rabeprazole sodium were negative. Consequently, she was diagnosed with AGEP. Systemic prednisolone was stopped 10 days after initiation and her rash disappeared 3 days later. Seventeen months later, her hepatitis worsened, and she required a liver transplantation and steroid administration. Results of a patch test performed with prednisolone 10%, betamethasone 10% and Vaseline (negative control) revealed a positive reaction to prednisolone after 24 and 72 h (Fig. 1d). Another patch test was performed with prednisolone sodium succinate, hydrocortisone, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, methylprednisolone, methylprednisolone sodium succinate, dexamethasone and dexamethasone sodium phosphate. In addition, a patch test was performed with medicinal substances of prednisolone, including lactose hydrate, corn starch and hydroxypropyl cellulose. Results of these patch tests were negative. We diagnosed this case as AGEP
(a)
(b)
(c)
(d)
Figure 1. (a) Clinical findings on the ventral side of the trunk. Red papules and scarlet colored edematous erythema are seen on the whole body. (b) Multiple pustules were observed on the erythematous plaques. (c) Histopathological examination revealed neutrophilic pustules under the stratum corneum, and lymphocytic, eosinophilic and neutrophilic infiltrates in the upper dermis (hematoxylin–eosin, original magnification 9400). (d) Patch test revealed a positive reaction to prednisolone after 24 h.
induced by prednisolone. Subsequently, methylprednisolone sodium succinate treatment was initiated for hepatitis, which was well tolerated. Corticosteroids, which are widely used because of their anti-inflammatory and immunosuppressive effects, have been reported to induce a variety of adverse drug reactions, including contact dermatitis. However, generalized hypersensitivity reactions after systemic administration of corticosteroids are rare.2 Reported cases of AGEP induced by corticosteroids are especially few. Although it has been reported that the sensitivity of patch testing to drugs in AGEP is approximately 50%,3,4 in this case, AGEP was successfully confirmed by patch test. The patient had never taken oral prednisolone, but had been treated with topical prednisolone ointment 10 years previously
Correspondence: Toshio Hasegawa, M.D., Ph.D., Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Email: [email protected]
© 2014 Japanese Dermatological Association
1135
Letters to the Editor
for acne. It is possible that she was previously sensitized to prednisolone by the ointment. We should be careful in using corticosteroids, because even prednisolone can cause drug eruption.
CONFLICT OF INTEREST:
None.
Satoko ISHII,1 Toshio HASEGAWA,1 Yusuke HIRASAWA,1 Yuichiro TSUNEMI,2 Makoto KAWASHIMA,2 Shigaku IKEDA1 1
Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, and 2Department of Dermatology, Tokyo Women’s Medical University, Tokyo, Japan
doi: 10.1111/1346-8138.12658
REFERENCES 1 Roujeau JC, Bioulac-Sage P, Bourseau C et al. Acute generalized exanthematic pustulosis: analysis of 63 cases. Arch Dermatol 1991; 127: 1333–1338. 2 Bircher AJ, Levy F, Langauer S, Lepoittevin JP. Contact allergy to topical corticosteroids and systemic contact dermatitis from prednisolone with tolerance of triamcinolone. Acta Derm Venereol 1995; 75: 490–493. 3 Demitsu T, Kosuge A, Yamada T. Acute generalized exanthematous pustulosis induced by dexamethasone injection. Dermatology 1996; 193: 56–58. 4 Mussot-Chia C, Flechet ML, Napolitano M et al. Methylprednisoloneinduced acute generalized exanthematous pustulosis. Ann Dermatol Venereol 2001; 128: 241–243.
Elevation of serum KL-6 levels during treatment with tumor necrosis factor-a inhibitor in patients with psoriasis Dear Editor, KL-6 is a serum biomarker for detection of various interstitial lung diseases.1 Herein, we investigated the correlation between biologic treatment and elevation of serum KL-6 levels in Japanese psoriatic patients. A total of 19 psoriatic patients whose serum KL-6 levels were measured before initiation of biologic therapy and followed up for at least 6 months were analyzed (Table 1). Serum KL-6 levels were measured using LUMIPULSEâ KL-6 Eisai or NANOPIAâ KL-6 Eisai (Eisia, Tokyo,
Japan) by in-house laboratory. Of these 19 patients, none showed an increase within the first year. In the patients who were followed up for more than a year, serum KL-6 levels exceeded the upper normal limit of 500 U/mL in three of seven patients treated with adalimumab. Mean serum KL-6 level at maximum during adalimumab therapy (376.9 268.6 U/mL) showed significant increase (P = 0.03, paired Student’s t-test). None had clinical symptoms or computed tomography scan findings of pneumonia. In contrast, elevation of serum KL-6
Table 1. Characteristics of the enrolled psoriatic patients Adalimumab‡ No. Sex Male (%) Female (%) Age at baseline† (years) Type of psoriasis Psoriasis vulgaris Psoriatic arthritis Generalized pustular psoriasis Follow-up period† (months) Serum KL-6 level at baseline† (U/mL) Serum KL-6 level at maximum† (U/mL) No. of patients whose serum KL-6 levels exceeded 500 U/mL Treatment history of methotrexate Past history of interstitial lung diseases
7
Infliximab 4
Ustekinumab§ 8
5 (71%) 2 (29%) 49.7 12.6
2 (50%) 2 (50%) 58.3 14.5
7 (88%) 1 (12%) 48.5 16.7
4 2 1 22.0 10.2 196.0 70.2 376.9 268.6 3
0 3 1 16.0 9.6 186.0 87.5 223.8 59.6 0
7 1 0 15.8 7.5 213.7 82.9 191.0 53.0 0
0 0
2¶ 0
0 0
† Mean standard deviation. ‡One case is a switcher from infliximab. §Two cases had history of previous infliximab treatment. ¶One case is treated with combination therapy. One case had history of previous treatment.
Correspondence: Tomotaka Mabuchi, M.D., Ph.D., Department of Dermatology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan. Email: [email protected]
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© 2014 Japanese Dermatological Association
