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.



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


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]


© 2014 Japanese Dermatological Association

Letters to the Editor

levels was not found in any of the patients treated with infliximab (n = 4) and ustekinumab (n = 8). Mean serum KL-6 levels at maximum during infliximab and ustekinumab therapies were 223.8  59.6 and 191.0  53.0 U/mL, respectively. There were no statistical significances between before and during treatments. A retrospective study of rheumatoid arthritis patients reported increases in serum KL-6 levels in nine (27.3%) of 33 patients treated with adalimumab, eight (18.0%) of 44 patients treated with infliximab and eight (16.0%) of 50 patients treated with etanercept at least once during the following year.2 At least 22 of these 25 patients had no apparent interstitial lung diseases.2 A clinical trial of infliximab in Japanese rheumatoid arthritis patients revealed that 48 (14.7%) of 327 patients had increased serum KL-6 levels without significant clinical events by week 54.3 KL-6 is a high-molecular-weight glycoprotein classified as a polymorphic epithelial mucin, and is highly expressed on the surface of type 2 pneumocytes.1 Circulating KL-6 in serum is thought to be derived from this expression.1 KL-6 is a submolecule of MUC1, thus KL-6/MUC1 is commonly used to denote the KL-6 molecule.1 The MUC1 extracellular domain can be shed into the pulmonary epithelial lining fluid (ELF) through the action of tumor necrosis factor (TNF)-a-converting enzyme (TACE), also known as a disintegrin and metalloproteinase 17 (ADAM17).1 The soluble form of TNF-a (sTNF-a), which is cleaved from transmembrane TNF-a (tmTNF-a) by TACE, mediates its biological activities through binding to type 1 and 2 TNF receptors (TNF-R1 and TNF-R2) of remote tissues.4 Although tmTNF-a also binds to TNF-R1 and TNF-R2, its biological activities function through mainly binding with TNF-R2.4 Upon binding to TNF receptors, both tmTNF-a and sTNF-a mediate pleiotropic effects, including cell proliferation and cytokine production.4 Infliximab binds to both tmTNF-a and

© 2014 Japanese Dermatological Association

sTNF-a, whereas adalimumab binds to tmTNF-a.4 In the presence of TNF-a inhibitors, overexpressed TACE may enhance the MUC1 extracellular domain shedding into ELF, therefore, serum KL-6 level could be increased. In conclusion, TNF-a inhibitors may increase serum KL-6 levels without the occurrence of interstitial lung diseases. In such a case, treatment with TNF-a inhibitors can be continued with careful observation.



Tomotaka MABUCHI, Hanako YAMAOKA, Mayu KAWAI, Tami OTA, Akira OZAWA Department of Dermatology, Tokai University School of Medicine, Isehara, Kanagawa, Japan doi: 10.1111/1346-8138.12681

REFERENCES 1 Ishikawa N, Hattori N, Yokoyama A et al. Utility of KL-6/MUC1 in the clinical management of interstitial lung diseases. Respir Investig 2012; 50: 3–13. 2 Takamura A, Hirata S, Nagasawa H et al. A retrospective study of serum KL-6 levels during treatment with biological disease-modifying antirheumatic drugs in rheumatoid arthritis patients: a report from the Ad Hoc Committee for Safety of Biological DMARDs of the Japan College of Rheumatology. Mod Rheumatol 2013; 23: 297–303. 3 Harigai M, Takamura A, Atsumi T et al. Elevation of KL-6 serum levels in clinical trials of tumor necrosis factor inhibitors in patients with rheumatoid arthritis: a report from the Japan College of Rheumatology Ad Hoc Committee for Safety of Biological DMARDs. Mod Rheumatol 2013; 23: 284–296. 4 Horiuchi T, Mitoma H, Harashima S et al. Transmembrane TNF-a: structure, function and interaction with anti-TNF agents. Rheumatology (Oxford) 2010; 49: 1215–1228.


Elevation of serum KL-6 levels during treatment with tumor necrosis factor-α inhibitor in patients with psoriasis.

Elevation of serum KL-6 levels during treatment with tumor necrosis factor-α inhibitor in patients with psoriasis. - PDF Download Free
99KB Sizes 2 Downloads 6 Views

Recommend Documents

Elevation of serum tumor necrosis factor α in patients with periprosthetic osteolysis: a case-control study.
Periprosthetic osteolysis is the leading reason for THA revision. The relationship of serum biomarkers with severe radiographic periprosthetic osteolysis has not been defined but may be important to direct future research and clinical therapeutics.

Relapsed Pulmonary Cryptococcosis during Tumor Necrosis Factor α Inhibitor Treatment.
A 35-year-old non-HIV patient developed pulmonary cryptococcosis after the initiation of infliximab. He recovered by fluconazole treatment and completed the therapy for a total of 6 months. However, he experienced a relapse 16 months later during ret

Increased serum tumor necrosis factor α levels in patients with lenalidomide-induced hypothyroidism.
As the use of lenalidomide expands, the poorly understood phenomenon of lenalidomide-induced thyroid abnormalities will increase. In this study, we compared rates of therapy-induced hypothyroidism in 329 patients with diffuse large B-cell lymphoma (D

Serum levels of adipocytokines in psoriasis patients receiving tumor necrosis factor-α inhibitors: results of a retrospective analysis.
Adipocytokines are bioactive molecules that are deeply involved in the occurrence of atherosclerosis, obesity, and autoimmune inflammatory diseases.

Serum irisin levels in patients with psoriasis.
Irisin has been proposed to regulate metabolic diseases such as obesity, diabetes or metabolic syndrome which are common comorbidities in psoriasis.

The risk of tuberculosis in patients with psoriasis treated with anti-tumor necrosis factor agents.
Tumor necrosis factor-alpha (TNF-α) antagonist treatment is associated with 1.6 to 27 times higher risk of tuberculosis (TB).

Periodontal and serum protein profiles in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitor adalimumab.
Tumor necrosis factor (TNF)-α inhibitor has been shown to affect the periodontal condition of patients with rheumatoid arthritis (RA). The aim of the present study is to assess the effect of a fully humanized anti-TNF-α monoclonal antibody, adalimuma

Serum Levels of Tumor Necrosis Factor-α and Interleukins in Children with Congenital Heart Disease.
Background: Levels of anti-inflammatory cytokines in blood have a positive relationship with congenital heart disease (CHD). We sought to assess the difference in serum cytokines levels between children with and without CHD.  Methods: We recruited 60

High Serum Tumor Necrosis Factor-Alpha Levels in Women with Polycystic Ovary Syndrome: A Meta-Analysis.
The objective of the study is to assess the TNF-α levels in PCOS patients and healthy controls. A comprehensive electronic search in Medline, Embase, and the Cochrane Library database was conducted up to July 2016. Random-effects model was used to es