The majority of generalized pustular psoriasis without psoriasis vulgaris is caused by deficiency of interleukin-36 receptor antagonist.

Generalized pustular psoriasis (GPP) is a rare inflammatory skin disease that can be life-threatening. Recently, it has been reported that familial GPP is caused by homozygous or compound heterozygous mutations of IL36RN. However, the majority of GPP cases are sporadic and it is controversial whether IL36RN mutations are a causative/predisposing factor for sporadic GPP. We searched for IL36RN mutations in two groups of GPP patients in the Japanese population in this study: GPP without psoriasis vulgaris (PV), and GPP with PV. Eleven cases of GPP without PV (GPP alone) and 20 cases of GPP accompanied by PV (GPP with PV) were analyzed. Surprisingly, 9 out of 11 cases of GPP alone had homozygous or compound heterozygous mutations in IL36RN. In contrast, only 2 of 20 cases of GPP with PV had compound heterozygous mutations in IL36RN. The two cases of GPP with PV who had compound heterozygous mutations in IL36RN are siblings, and both cases had PV-susceptible HLA-A*0206. We determined that GPP alone is a distinct subtype of GPP and is etiologically distinguished from GPP with PV, and that the majority of GPP alone is caused by deficiency of the interleukin-36 receptor antagonist due to IL36RN mutations.

Acral pseudolymphomatous angiokeratoma of children: a case report with immunohistochemical study of antipodoplanin antigen.

Acral pseudolymphomatous angiokeratoma of children (APACHE) is characterized by multiple angiomatous papules on the hands and feet in children. Here, we report a case of APACHE in a female patient followed up from 13 to 19 years of age with a dark red lesion on the center of the dorsum of the right thigh. Histologically, vacuolar alteration and exocytosis of lymphocytes, and specific dense cellular infiltration beneath the epidermis to the reticular dermis were found. On immunolabeling study, the lesion vessels were found to be positive for both the lymphatic endothelium-specific marker podoplanin and blood vessel-specific marker CD34. These findings suggested that APACHE is a type of vascular malformation.

Cold-induced sweating syndrome with neonatal features of Crisponi syndrome: longitudinal observation of a patient homozygous for a CRLF1 mutation.

Cold-induced sweating syndrome (CISS) is a rare autosomal recessive disorder caused by mutations in CRLF1 (cytokine receptor-like factor 1), characterized by profuse sweating in cold environmental temperature and craniofacial and skeletal features. Mutations in CRLF1 also cause Crisponi syndrome (CS), characterized by neonatal-onset paroxysmal muscular contractions as well as craniofacial and skeletal manifestations and abnormal functions of the autonomic nerve system. To date, it is an unresolved problem whether the two conditions are distinct clinical entities or a single clinical entity with variable expressions or with different presentations depending on the patients' age at diagnosis. We report on a 30-year-old Japanese woman with CISS and homozygous out-of-frame 23-base deletion of CRLF1. In infancy, she did not show paroxysmal muscular contractions, but showed feeding difficulty, hyperthermia, and facial characteristics including thick and arched eyebrows, a short nose with anteverted nostrils, full cheeks, an inverted upper lip, and a small mouth, resembling those observed in CS. Profuse sweating was noticed at 3 years of age. Cold-induced sweating was recognized in her elementary school days. In adolescence to adulthood, she showed a Marfanoid habitus with progressive kyphoscoliosis and craniofacial characteristics including dolichocephaly, a slender face with poor expression, a distinctive nose with hypoplastic nares, malar hypoplasia, prognathism, and a small mouth. This is the first report of detailed longitudinal observation of a patient with CRLF1 abnormalities, compatible with the notion that CISS and CS may be a single clinical entity.

Histopathological characteristics of malignant melanoma affecting mucous membranes: a unifying concept of histogenesis.

AIMS: To investigate histopathological characteristics of melanocytic lesions affecting mucous membranes in various anatomical sites. Particular attention was paid to elucidation of morphological characteristics of early phases of mucosal melanoma in order to contribute to effective detection of this highly malignant neoplasm in the curable stages. METHODS: A total of 87 melanocytic lesions of mucous membranes were investigated histopathologically. There were 55 malignant melanomas including eight lesions of melanoma in situ, three in the radial growth phase (RGP) and 44 in the vertical growth phase (VGP), and 28 benign melanocytic lesions including four melanotic macules, 19 melanocytic naevi and five blue naevi. In addition, this series also included four equivocal lesions for which diagnoses were not definitely determined. With regard to malignant melanoma, histopathological patterns of in situ phase and RGP were intensely evaluated. RESULTS: Histopathological features of benign melanocytic lesions were essentially the same as those of the corresponding lesions of the skin. In the vast majority of mucosal melanomas, irrespective of anatomical sites, the main histopathological pattern seen in melanoma in situ and in RGP was the lentiginous pattern, which shows proliferation of atypical melanocytes in the lower layer of more or less acanthotic epithelium, though subtle variations of the pattern were detected. No association of melanocytic naevus was detected in any cases of melanoma. Based on these findings, we have proposed a unifying concept of de novo histogenesis of mucosal malignant melanoma. CONCLUSIONS: Our concept of histogenesis of mucosal melanoma assists in the identification of this highly malignant neoplasm in the early curable stages.