A case of IgA pemphigus with acantholysis in oral mucosal lesions.

IgA pemphigus is an autoimmune bullous disease caused by anti-keratinocyte cell surface IgA autoantibodies. Mucous membrane involvement is rare in IgA pemphigus. We report a case of IgA pemphigus with oral mucosal lesions, in which acantholysis was pathologically confirmed. A 31-year-old woman presented with skin erythema with small pustules and oral mucosal erosions. Histopathological examination of the erosions on her oral mucosa and papules on her back revealed acantholysis and intraepidermal infiltration of neutrophils. Direct immunofluorescence tests showed intercellular deposition of IgA, but not IgG, mainly in the lower, but not entire, layer of the epidermis. C3 was linearly present in the basement membrane zone (BMZ), but not in the intercellular space. Enzyme-linked immunosorbent assay revealed that both anti-desmoglein (Dsg) 3 IgA and IgG were positive. Neither IgA nor IgG against desmocollin 1-3 were detected. This case was clinically and histologically compatible with IgA pemphigus, but immunologically anti-BMZ autoimmunity was additionally observed. IgA pemphigus is classified into two major types: subcorneal pustular dermatosis type and intraepidermal neutrophilic dermatosis type. This case was not typical in terms of rarely observed oral lesions and predominant deposition of IgA in the lower layer of the epidermis. Instead, this case could be considered a rare subtype of IgA pemphigus, IgA-pemphigus vulgaris. Oral lesions in IgA pemphigus may be clinical clue of having anti-Dsg3 IgA that cannot be routinely examined.

[A CHILD CASE OF DIFFUSE CUTANEOUS MASTOCYTOSIS].

Cutaneous mastocytosis (CM) usually appears in childhood and improves substantially before adolescence. The c-KIT mutation of D816V is present in 36% and 20% of patients with childhood-onset CM and diffuse cutaneous mastocytosis (DCM), respectively. In some cases of childhood-onset DCM, the disease can progress to systemic mastocytosis; in others, it resolves spontaneously. Thus, assessing the prognosis is difficult. Herein, we described a case of DCM in an 11-month-old, male patient without a c-KIT mutation. The patient presented with dark brown macules and sporadic erythema topped by bullous lesions. A skin biopsy of the macule on the abdomen revealed accumulation of mast cells which were round to oval-shaped with amphophilic cytoplasm within the upper dermis. The patient had received H1 inhibitor until age 3 years and continued to experience blisters on the trunk. However, no severe symptoms, such as anaphylaxis, occurred. Included in this manuscript is a review of previous reports of childhood-onset DCM in Japan and cases specifically seen at our dermatology clinic.

Family with Legius syndrome (neurofibromatosis type 1-like syndrome).

Legius syndrome (Online Mendelian Inheritance in Man no. 611431) or neurofibromatosis type 1 (NF1)-like syndrome was first reported by Legius et al. in 2007. We herein report the first instance of Legius syndrome occurring in two female siblings in Japan. Both individuals presented cafe-au-lait macules and freckling. Mutation analysis revealed a mutation of c.349C>T resulting in p.Arg117* in the SPRED1 gene as the cause of the Legius syndrome. The National Institutes of Health criteria for NF1 are insufficient to rule out the condition. For this reason, and because the clinical course of each condition is quite different, we stress the need to differentiate Legius syndrome from NF1 clearly.

Clinical significance of blood coagulation factor XIII activity in adult Henoch-Schönlein purpura.

BACKGROUND: A correlation between decreased blood coagulation factor XIII activity and the severity of organ disorders in pediatric Henoch-Schönlein purpura (HSP) has been demonstrated, but possible correlations in adult HSP have not been thoroughly investigated. OBJECTIVES: To investigate the association between factor XIII activity with varying clinical severities of HSP and the severity of organ disorders and to examine the efficacy of factor XIII substitution therapy. METHODS: The distribution of purpura and the severities of joint, abdominal, and renal symptoms were scored in 44 adults with HSP. Plasma factor XIII activity was measured with the latex agglutination immunoturbidity method. RESULTS: Reduced factor XIII activities were correlated with clinical severity scores (the total of all scores), organ disorder severity scores (the total score excluding the purpura score), joint symptom scores, and abdominal symptom scores but not with renal disorder scores. Factor XIII activities were increased in patients during posttreatment remission. Factor XIII substitution therapy was performed in 7 patients with severe organ disorders. Consequently, joint and abdominal symptoms markedly improved, but renal symptoms did not. CONCLUSION: Measurement of plasma factor XIII activity in adult HSP is clinically useful because it indicates disease severity and the severity of digestive tract and joint disorders. Factor XIII substitution therapy is effective for joint and abdominal symptoms but not for renal symptoms. Further investigation of the effect of this treatment on renal symptoms is necessary.

A laminin-collagen complex drives human epidermal carcinogenesis through phosphoinositol-3-kinase activation.

Laminin-332 (formerly laminin-5) and collagen VII are basement membrane proteins expressed at the invasive front of human squamous cell carcinoma (SCC) tumors. These proteins have protumorigenic properties, but whether laminin-332 and collagen VII promote SCC tumors by providing adhesion or other nonadhesive extracellular cues, or whether laminin-332 and collagen VII interact together in this process remains unknown. In this study, we examined the role of these molecules by a structural approach using an in vivo model of human SCC tumorigenesis. Here, we show that individual domains (VI and V-III) on the laminin-332 beta3 chain provide distinct and highly divergent cell adhesion and tumor-promoting functions. We found that laminin beta3 domain VI provided a critical role in the assembly of stable adhesion complexes, but this domain was not required in SCC tumors. Instead, we found that laminin beta3 domain V-III played an essential role in SCC carcinogenesis/invasion through binding to collagen VII, which in turn, led to phosphoinositol-3-kinase activation and protection from apoptosis. Overexpression of constitutively active p110 phosphoinositol-3-kinase subunit was sufficient to restore invasion and tumorigenesis in transformed cells lacking laminin-332/collagen VII interaction in a manner independent of cellular adhesion. These studies show distinctive adhesive and signaling functions in individual domains of laminin-332, one which is required for normal epithelial adhesion and one which is required for SCC tumorigenesis. This uncoupling of stable adhesion from tumor progression in our studies suggests that laminin-332/collagen VII interaction promotes epidermal carcinogenesis through signaling rather than adhesion.

Genetic aspects of the vascular type of Ehlers-Danlos syndrome (vEDS, EDSIV) in Japan.

BACKGROUND: The vascular type of Ehlers-Danlos syndrome (vEDS, EDS type IV; MIM#130050) is an autosomal dominantly inherited disorder that results from mutations in the genes for type III procollagen (COL3A1). Affected individuals with vEDS are at risk of arterial rupture, aneurysm, and/or dissection; gastrointestinal perforation or rupture; and uterine rupture during pregnancy, which may lead to sudden death. METHODS AND RESULTS: Three unrelated Japanese individuals who exhibited symptoms of vEDS were analyzed. In order to identify mutations in the patients' RNA, one 3.8-kb reverse transcriptase polymerase chain reaction product containing the triple-helical domain of COL3A1 was prepared from cultured skin fibroblasts and then was sequenced directly. Three heterozygous mutations were identified; specifically, 2 novel missense base substitutions (Gly220Trp, Gly448Glu) in the (Gly-X-Y)n repeat of the triple-helical domain and a known splicing donor mutation of intron 20 (G+1, IVS20) of COL3A1. The genotype-phenotype correlations in Japanese vEDS individuals with COL3A1 mutations were also investigated. CONCLUSION: There was no association between the type of complications in vEDS and the related COL3A1 mutation found. After the genetic diagnosis of COL3A1, the establishment of both a network among medical specialists, including clinical geneticists to perform genetic counseling, and long-term follow-up systems of vEDS may help to improve the management of vascular and visceral complications.

A case of hypereosinophilic syndrome.

A 22-year-old man developed papules on his legs in November of 2001, which then spread to cover almost his entire body. He was treated with a topical steroid and PUVA therapy at another hospital. The symptoms showed no improvement, and, in February of 2002, he came to our hospital. Examination revealed hypereosinophilia, and, because he had symptoms of organ involvement by the heart, lung, and inguinal lymph nodes as well as the skin, we diagnosed him with idiopathic hypereosinophilic syndrome (HES). The patient was treated with oral prednisolone at a dose of 60 mg/day, and his cutaneous lesions and other organ symptoms improved.

Selective transduction of HIV-1-infected cells by the combination of HIV and MMLV vectors.

Human immunodeficiency virus 1 (HIV-1)-infected cells are important targets of gene therapy for acquired immune deficiency syndrome. We have developed a novel strategy for targeted gene transfer into HIV-1-infected cells based on 2-step gene transfer. The first step involves the stable introduction of the HIV vector containing the ecotropic Moloney murine leukemia virus (MMLV) receptor gene (EcoRec) into human CD4+ T cells as a molecular switch. Because the HIV-long terminal repeat (HIV-LTR) is Tat inducible, it is expected that EcoRec is expressed only after HIV-1 infection. Northern blot analysis and a retrovirus binding assay confirmed that the HIV-LTR of the integrated vector was silent in transduced cells but strongly transactivated in HIV-1 infection. High levels of EcoRec expression were observed only in HIV-1-infected cells. These cells became highly susceptible to ecotropic MMLV infection and, therefore, in the second step, HIV-1-infected cells were selectively transduced with ecotropic MMLV vectors. More than 70% of HIV-1-infected cells were transduced by this strategy. These findings indicate that this 2-step method can be used for selective and stable gene transfer into HIV-1-infected cells.