PMID- 32157724
OWN - NLM
STAT- MEDLINE
DCOM- 20210208
LR  - 20210208
IS  - 1346-8138 (Electronic)
IS  - 0385-2407 (Linking)
VI  - 47
IP  - 5
DP  - 2020 May
TI  - Abnormal keratinization and cutaneous inflammation in Mal de Meleda.
PG  - 554-558
LID - 10.1111/1346-8138.15296 [doi]
AB  - Mal de Meleda (MDM) is a rare, autosomal recessive form of palmoplantar 
      keratoderma due to mutations in the gene, encoding for secreted lymphocyte 
      antigen 6/urokinase-type plasminogen activator receptor related protein 1 
      (SLURP1). We report a four-year-old Taiwanese MDM female case whose biopsy 
      specimen of hyperkeratotic lesions showed abnormal keratinization and cutaneous 
      inflammation with characteristic transmission electron microscopic (TEM) findings 
      and immunostaining results. The patient presented with pruritic and severely 
      hyperkeratotic plaques on the bilateral palms and soles whichwere fringed with 
      erythematous scaly areas. A homozygous c.256 G>A mutation, predicting a 
      conversion of p.Gly86Arg, in SLURP1gene was detected. Histopathological 
      examinations showed marked hyperkeratosis, acanthosis and hypergranulosis in the 
      epidermis, accompanied by perivascular lymphocytic infiltrates in the dermis. The 
      whole layers of the epidermis and perivascular infiltrates of the dermis were 
      stained positive with anti-tumor necrosis factor alpha (TNFalpha) antibody in the 
      biopsy specimen from the sole and the ankle. TEM examination of the biopsy 
      specimen from the plantar hyperkeratotic plaque showed various-sized vacuoles 
      surrounding nuclei of many keratinocytes in the spinous layer. In addition, there 
      were numerous irregular keratohyaline granules in the granular layer. Several 
      microorganisms and many lipid-like droplets were found in the thickened cornified 
      layer. SLURP1 protein is known as a marker of late differentiation, predominantly 
      expressed in the granular layer, and also known to have an inhibitory effect on 
      TNFalpha release. Our results exhibited excessive TNFalpha expression in keratinocytes 
      and perivascular infiltrates of the dermis, and several characteristic 
      morphological observations of keratinocytes in MDM.
CI  - (c) 2020 Japanese Dermatological Association.
FAU - Kudo, Mari
AU  - Kudo M
AD  - Department of Dermatology, National Center for Global Health and Medicine, Tokyo, 
      Japan.
FAU - Ishiura, Nobuko
AU  - Ishiura N
AUID- ORCID: 0000-0003-2354-0811
AD  - Department of Regenerative Medicine, Research Institute, National Center for 
      Global Health and Medicine, Tokyo, Japan.
AD  - Department of Dermatology, Japan Community Health Care Organization Tokyo 
      Shinjuku Medical Center, Tokyo, Japan.
FAU - Tamura-Nakano, Miwa
AU  - Tamura-Nakano M
AD  - Department of Regenerative Medicine, Research Institute, National Center for 
      Global Health and Medicine, Tokyo, Japan.
FAU - Shimizu, Teruo
AU  - Shimizu T
AD  - Department of Dermatology, Teikyo University Graduate School of Medicine, Tokyo, 
      Japan.
FAU - Kamata, Masahiro
AU  - Kamata M
AD  - Department of Dermatology, Teikyo University Graduate School of Medicine, Tokyo, 
      Japan.
FAU - Akasaka, Eijiro
AU  - Akasaka E
AUID- ORCID: 0000-0003-0866-8032
AD  - Department of Dermatology, Hirosaki University Graduate School of Medicine, 
      Hirosaki, Japan.
FAU - Nakano, Hajime
AU  - Nakano H
AD  - Department of Dermatology, Hirosaki University Graduate School of Medicine, 
      Hirosaki, Japan.
FAU - Okuma, Yoshiaki
AU  - Okuma Y
AD  - Department of Pediatrics, National Center for Global Health and Medicine, Tokyo, 
      Japan.
FAU - Tada, Yayoi
AU  - Tada Y
AD  - Department of Dermatology, Teikyo University Graduate School of Medicine, Tokyo, 
      Japan.
FAU - Okochi, Hitoshi
AU  - Okochi H
AD  - Department of Regenerative Medicine, Research Institute, National Center for 
      Global Health and Medicine, Tokyo, Japan.
FAU - Tamaki, Takeshi
AU  - Tamaki T
AD  - Department of Dermatology, National Center for Global Health and Medicine, Tokyo, 
      Japan.
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20200310
PL  - England
TA  - J Dermatol
JT  - The Journal of dermatology
JID - 7600545
RN  - 0 (Antigens, Ly)
RN  - 0 (SLURP1 protein, human)
RN  - 0 (TNF protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Antigens, Ly/*genetics
MH  - Biopsy
MH  - Child, Preschool
MH  - DNA Mutational Analysis
MH  - Female
MH  - Foot
MH  - Hand
MH  - Homozygote
MH  - Humans
MH  - Keratinocytes/immunology/*pathology
MH  - Keratoderma, Palmoplantar/*diagnosis/genetics/immunology/pathology
MH  - Microscopy, Electron, Transmission
MH  - Mutation
MH  - Pedigree
MH  - Skin/cytology/*immunology/pathology/ultrastructure
MH  - Tumor Necrosis Factor-alpha/immunology/metabolism
MH  - Urokinase-Type Plasminogen Activator/*genetics
OTO - NOTNLM
OT  - Mal de Meleda
OT  - palmoplantar keratoderma
OT  - secreted lymphocyte antigen 6
OT  - tumor necrosis factor-alpha
OT  - urokinase-type plasminogen activator receptor-related protein 1
EDAT- 2020/03/12 06:00
MHDA- 2021/02/09 06:00
CRDT- 2020/03/12 06:00
PHST- 2019/05/18 00:00 [received]
PHST- 2020/02/09 00:00 [accepted]
PHST- 2020/03/12 06:00 [pubmed]
PHST- 2021/02/09 06:00 [medline]
PHST- 2020/03/12 06:00 [entrez]
AID - 10.1111/1346-8138.15296 [doi]
PST - ppublish
SO  - J Dermatol. 2020 May;47(5):554-558. doi: 10.1111/1346-8138.15296. Epub 2020 Mar 
      10.