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 (TNFα) 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 TNFα release. Our results exhibited excessive TNFα expression in keratinocytes and perivascular infiltrates of the dermis, and several characteristic morphological observations of keratinocytes in MDM.

The formation and deposition of immune complexes (IC) containing immunoglobulin (Ig)G antibodies induces an acute inflammatory response with tissue injury. One of the experimental models of IC‐related vasculitis is the cutaneous reverse passive Arthus reaction, in which IgG antibodies are injected i.d., followed immediately by the i.v. application of the corresponding antigen. This reaction is characterized by edema, hemorrhage and neutrophil infiltration. To assess the role of the anti‐inflammatory cytokine interleukin (IL)‐10 in IC‐related vasculitis, we investigated the cutaneous Arthus reaction using IL‐10 knockout (IL‐10KO) mice. Edema, which was quantified macroscopically by measuring the vascular leakage of Evans blue dye at 4 h after IC challenge, was significantly increased in IL‐10KO mice compared with wild‐type mice. In addition, hemorrhage, which was assessed by the average diameter of purpuric spots at 8 h after IC challenge, was enhanced significantly in IL‐10KO mice compared with wild‐type mice. Histological examination showed that the number of extravascular neutrophils was significantly increased in IL‐10KO mice compared with wild‐type mice at 4 and 8 h after IC challenge. Analysis of pro‐inflammatory cytokine mRNA expression showed that IL‐6 mRNA levels were significantly increased in IL‐10KO mice compared with wild‐type mice at 4 and 8 h after IC challenge. These results showed that IC‐induced inflammation and vascular damage were significantly enhanced in the absence of IL‐10. Thus, IL‐10 may limit tissue disruption by suppressing the excessive infiltration of neutrophils and cytokine expression in a mouse model of type III vasculitis.