Kazuko C. Sato-Matsumura

Kikuchi's disease and the skin: case report and review of the literature

We report scattered indurated erythematous lesions that presented in an 18‐year‐old Japanese man with Kikuchis disease (KD; histiocytic necrotizing lymphadenitis). A skin biopsy showed a proliferation of histiocytes and abundant nuclear debris without the presence of neutrophils, which is characteristic of KD. The specific dermatological and pathological details of KD have been yet to be fully described. In order to assess the typical skin features of KD better, we have reviewed all the previously well‐documented reports of such lesions. As the clinical and histopathological cutaneous findings in KD are so heterogeneous, it is important that scattered indurated erythematous lesions should be included as one of the possible cutaneous manifestations of this disease.

Transformation-specific matrix metalloproteinases (MMP)-7 and MMP-13 are expressed by tumour cells in epidermolysis bullosa-associated squamous cell carcinomas

Background  Patients with recessive dystrophic epidermolysis bullosa (RDEB) have an increased risk of developing rapidly progressive and metastatic cutaneous squamous cell carcinomas (SCC). It is unclear why these SCC behave more aggressively than sporadic SCC. Matrix metalloproteinases (MMP) are a family of endopeptidases that contribute to growth, invasion and metastasis of SCC. The role of MMP in RDEB‐associated SCC is not known.

Distribution of IL-18 and IL-18 receptor in human skin: various forms of IL-18 are produced in keratinocytes.

Abstract Human interleukin-18 (IL-18) enhances IL-12-mediated IFN-γ production by lymphocytes and Fas/ perforin-mediated cytolysis by NK cells. IL-18 is synthesized as a 24 kDa proform, and the proform is processed in the cytoplasm into an 18 kDa mature form. Active and precursor forms of IL-18 have been detected in immunocompetent cells, and active IL-18 exerts its functions through its receptor. We sought to determine which human skin cells are responsible for production of IL-18 and which express its receptor. Monoclonal antibodies against human IL-18 and polyclonal antibody against IL-18 receptor were provided for this analysis. Formalin-embedded and frozen sections of human epidermis were analyzed by immunoperoxidase and immunofluorescence staining. IL-18 was detected in all living cell layers of the epidermis, hair follicles, arrectores pilorum, eccrine ducts and endothelial cells. IL-18 was localized in the cytoplasm of cells in living epidermal cell layers. In contrast, IL-18 receptor was mainly detected in keratinocytes and expressed in the cell periphery in living cell layers. Since keratinocytes were the main source of IL-18 and its receptor, cultured human keratinocytes were further analyzed by immunoblotting. IL-18 receptor was identified as an 80 kDa single band. The mature 18 kDa and precursor 24 kDa forms of IL-18 were detected by our monoclonal antibody (mAb) 21 and mAb 132, respectively, while only the 18 kDa form was detected by a commercial mAb, 125-2H. Cultured keratinocytes showed positive granular staining for IL-18 in the cytoplasm and positive staining for IL-18 receptor mainly in the cell periphery. Our findings indicate that mature IL-18, precursor IL-18 and IL-18 receptor are simultaneously expressed with different localizations by human epidermal keratinocytes. Keratinocytes might be activated by their own IL-18 in an autocrine or paracrine fashion.

Genetic studies of 20 Japanese families of dystrophic epidermolysis bullosa

AbstractDystrophic EB (DEB) is clinically characterized by mucocutaneous blistering in response to minor trauma, followed by scarring and nail dystrophy, and is caused by mutations in the COL7A1 gene encoding type VII collagen. DEB is inherited in either an autosomal dominant (DDEB) or recessive (RDEB) fashion. DDEB basically results from a glycine substitution mutation within the collagenous domain on one COL7A1 allele, while a combination of mutations such as premature stop codon, missense, and splice-site mutations on both alleles causes RDEB. In this study, mutation analysis was performed in 20 distinct Japanese DEB families (16 RDEB and four DDEB). The result demonstrated 30 pathogenic COL7A1 mutations with 16 novel mutations, which included four missense, five nonsense, one deletion, two insertion, one indel, and three splice-site mutations. We confirmed that Japanese COL7A1 mutations were basically family specific, although three mutations, 5818delC, 6573+1G>C, and E2857X, were recurrent based on previous reports. Furthermore, the Q2827X mutation found in two unrelated families would be regarded as a candidate recurrent Japanese COL7A1 mutation. The study furthers our understanding of both the clinical and allelic heterogeneity displayed in Japanese DEB patients.

Ichthyosis follicularis with alopecia and photophobia in a mother and daughter

A mother and daughter having ichthyosis follicularis with alopecia and photophobia (IFAP) are reported, with histopathological and electron microscopic findings. We have followed the clinical course of the mother for 26 years since she was 5 years old, and the daughter since birth. They have had almost all the classical and some of the minor symptoms of IFAP, including severe photophobia, extensive non‐inflammatory follicular hyperkeratosis, generalized non‐scarring alopecia, hyperkeratosis of the extensor aspect of the four extremities, nail deformity and recurrent cheilitis. In addition, their facial appearance greatly resembles that of previously reported patients. A consistent feature in the mother was florid keratotic inflammatory eruptions on the genital region during each of her pregnancies, which rapidly improved after the delivery. Skin biopsy of the genital lesion showed marked acanthosis with dyskeratosis and spongiotic changes. The electron microscopic examination of diseased skin showed damaged desmosomes with spongiosis. No obvious changes were found in normal appearing skin.

Rapid remission of severe pruritus from angiolymphoid hyperplasia with eosinophilia by pulsed dye laser therapy.

A 48‐year‐old Japanese woman with angiolymphoid hyperplasia with eosinophilia (ALHE) was successfully treated with a flashlamp pulsed dye laser (585 nm, 450 µs pulse duration). The lesion was severely pruritic and had been enlarging slowly for 2 years but was resistant to conventional therapies, including topical, intralesional, and systemic corticosteroid, and cryotherapy. The severe pruritus immediately improved after the first treatment using the pulsed dye laser. The erythema and papules gradually improved without scarring and this was followed by further five treatments over approximately a 4‐month interval. No clinical recurrences have been observed 1 year after completion of the treatment. We think that pulsed dye laser therapy is an effective treatment for ALHE in both Japanese as well as Caucasian patients. Pulsed dye laser therapy is also helpful in reducing the pruritus in ALHE patients.

Immunological Reconstitution after Autologous Hematopoietic Stem Cell Transplantation in Patients with Systemic Sclerosis: Relationship Between Clinical Benefits and Intensity of Immunosuppression

Objective. To analyze the relationship between clinical benefits and immunological changes in patients with systemic sclerosis (SSc) treated with autologous hematopoietic stem cell transplantation (HSCT). Methods. Ten patients with SSc were treated with high-dose cyclophosphamide followed by highly purified CD34+ cells (n = 5) or unpurified grafts (n = 5). Two groups of patients were retrospectively constituted based on their clinical response (good responders, n = 7; and poor responders, n = 3). As well as clinical findings, immunological reconstitution through autologous HSCT was assessed by fluorescence-activated cell sorter analysis, quantification of signal joint T cell receptor rearrangement excision circles (sjTREC), reflecting the thymic function, and foxp3, a key gene of regulatory T cells, mRNA levels. Results. Patients’ clinical and immunological findings were similar between good and poor responders, or CD34-purified and unpurified groups at inclusion. The sjTREC values were significantly suppressed at 3 months after autologous HSCT in good responders compared with poor responders (p = 0.0152). Reconstitution of CD4+CD45RO− naive T cells was delayed in good responders compared with poor responders. The phenotype of other lymphocytes, cytokine production in T cells, and foxp3 gene expression levels after autologous HSCT did not correlate with clinical response in good or poor responders. Clinical and immunological findings after autologous HSCT were similar between CD34-purified and unpurified groups. Conclusion. Our results suggest that immunosuppression intensity, sufficient to induce transient suppression of thymic function, is attributable to the feasible clinical response in patients with SSc treated with autologous HSCT. Appropriate monitoring of sjTREC values may predict clinical benefits in transplanted SSc patients after autologous HSCT.

Leukaemic dissemination of Merkel cell carcinoma in a patient with systemic lupus erythematosus

We describe an unusual bone‐marrow metastasis of Merkel cell carcinoma (MCC) arising in the right cheek of a 73‐year‐old woman with systemic lupus erythematosus (SLE) and Sjögren’s syndrome, who had been treated with oral prednisolone and methotrexate for 10 years. Seven months after wide local excision followed by local irradiation, the patient presented with thrombocytopaenia. Her bone marrow had been completely replaced by metastatic MCC cells, and metastatic cytokeratin 20‐positive cells were also identified in the peripheral blood. To our knowledge, in the English literature, only six cases have been described previously of MCC bone‐marrow involvement. Of these six cases, four were immunosuppressed, similar to our case. The high incidence of MCC in immunosuppressed patients such as those with SLE has been discussed previously. We consider that immunosuppression might be associated with bone‐marrow metastasis, which is a rare form of MCC.

Two cases of pyoderma gangrenosum complicated with nasal septal perforation

We report two patients with pyoderma gangrenosum complicated with nasal septal perforation. An 18‐year‐old woman and a 65‐year‐old man had typical lesions of pyoderma gangrenosum on the legs that responded well to oral prednisolone. Both patients complained of mild nasal discharge, and nasal fibroscopy revealed nasal septal perforation. Biopsy of the nasal lesions showed an active inflammatory infiltrate, mainly of neutrophils. Systemic investigations failed to show any pulmonary or renal lesions of Wegener’s granulomatosis. Cytoplasmic immunofluorescent pattern antineutrophil cytoplasmic antibody was negative. In both cases, intense neutrophilic infiltration was observed not only in skin lesions but also in nasal lesions, which may indicate that the nasal lesions had a pathogenesis in common with the skin lesions.

Serological and immunohistochemical detection of human herpesvirus 8 in Kaposi's sarcoma after immunosuppressive therapy for bullous pemphigoid

Kaposis sarcoma (KS) developed in an 87‐year‐old human immunodeficiency virus‐negative woman from Hokkaido island 4 months after oral administration of prednisolone for the treatment of bullous pemphigoid (BP), and rapidly disseminated to almost the entire body within 2 months. The open reading frame (ORF) 59 and ORF73 proteins encoded by human herpesvirus 8 (HHV‐8) were detected immunohistochemically in the nuclei of the tumour cells of KS. The protein coded by ORF73, latent protein, was detected in most of the nuclei of the tumour cells, but only a few tumour nuclei were positive for the ORF59 protein, a lytic protein expressed during active infection. The antibodies against both lytic and latent proteins of HHV‐8 were detected retrospectively in the serum 4 months before the appearance of KS and before prednisolone therapy had been started. Immunosuppression associated with the treatment for BP possibly activated latent HHV‐8 infection and induced the development of KS.