Paraneoplastic pemphigus presenting as mild cutaneous features of pemphigus foliaceus and lichenoid stomatitis with antidesmoglein 1 antibodies.

Herein, we report a case of paraneoplastic pemphigus with mild skin features of pemphigus foliaceus and lichenoid stomatitis associated with B-cell lymphoma. A 49-year-old man presented with scattered blisters and erosions on the trunk along with mucosal blisters and erosions. Skin biopsy showed subcorneal acantholytic bulla and oral mucosal biopsy demonstrated lichenoid dermatitis. Direct immunofluorescence showed cell surface deposits of IgG and C3. Indirect immunofluorescence identified circulating IgG autoantibodies to the cell surfaces of normal human skin and also on the transitional epithelium of rat bladder. Enzyme-linked immunosorbent assay using recombinant baculoproteins showed positive antidesmoglein 1 autoantibodies (index 46) but negative antidesmoglein 3 autoantibodies (index 8). Immunoblot analysis using normal human epidermal extract detected BP230 and the 190 kDa periplakin, while immunoprecipitation using radiolabeled cultured keratinocyte immunoprecipitated BP230 and the 210 kDa envoplakin. We consider that the skin lesion was produced by humoral immunity whereas the oral lesion was produced by cellular immunity.

Pretibial dystrophic epidermolysis bullosa with localized cutaneous amyloidosis: coincidental or secondary amyloidosis?

Here, we describe the case of a patient with pretibial dystrophic epidermolysis bullosa (PDEB) with amyloid deposition. The patient was a 40-year-old Japanese woman who presented a blistering eruption in the pretibial area with flat violaceous-brown lichenoid papules. The histology of the blister revealed a subepidermal bulla with antibodies bound to basement membrane antigens on the blister roof by immunoflourescent mapping. Electron microscopy revealed a blister cleavage plane below the lamina densa. The histology of the lichenoid papules showed amyloid deposition in the papillary dermis. Because it was confined to just beneath the bulla base of the blister specimen, the amyloid deposition may have been derived from degenerated keratinocytes induced by damage to the epidermal-dermal junction due to blister formation in PDEB in this case. PDEB, in general, is often misdiagnosed as lichen amyloidosis; however, some PDEB cases could actually be associated with amyloid deposition.

Clinical features of antinuclear antibody-positive patients with atopic dermatitis.

Twenty to thirty percent of patients with atopic dermatitis (AD) are positive for antinuclear antibodies (ANAs). In this study we investigated the prevalence of ANA in 100 patients with AD and examined the difference between ANA-positive (ANA+) and ANA-negative (ANA(-)) patients with AD. ANAs were identified with indirect immunofluorescence on Hep-2 cells. Nineteen patients (19%) with AD were found to be positive for ANAs at titers ranging from 1 : 40 to 1 : 640. The rate of ANA positivity in male patients (20.4%) was higher than that in female patients (17.6%). The rate of ANA positivity differed significantly between patients with AD and healthy control subjects (p=0.0001, odds ratio: 2.8). There was also a relationship between ANA+ AD and photosensitivity in male subjects (p=0.0346). The ANA+ patients with AD showed higher levels of cedar pollen-specific IgE than did ANA(-) patients (p=0.0232). In ANA+ patients disease severity was correlated with basophil counts (r=0.513, p=0.0344) and serum LDH levels (r=0.741, p=0.0056). The results indicate that patients with AD who are positive for ANA are a subpopulation of patients with AD.

Basal cell carcinoma arising on a chronic lymphedematous leg.

We describe a case of an 82-year-old Japanese woman with basal cell carcinoma (BCC) on the leg with secondary chronic lymphedema due to treatment for uterine cancer. Sparse tumor nests with remarkable edema of the dermis in the nodule appeared to be influenced by the chronic lymphedema. However, it remains inconclusive whether or not the tumorigenesis of the BCC was associated with chronic lymphedema in this case.

Identification of 6 sentinel lymph nodes in a case of malignant melanoma on the ungual region of the finger.

We describe a case of malignant melanoma on the ungual region of the index finger with which 6 sentinel lymph nodes were detected in the axillary basin. Of these nodes, 1 of 3 brachial nodes and 2 of 3 central axillary nodes showed micrometastasis. Additional lymph nodes obtained at the subsequent complete axillary lymph node dissection showed no metastasis. Identification of as many as 6 sentinel lymph nodes was ascribed to a single lymph trunk that would branch off to afferent lymphatics draining to each nodal group; however, a gamma probe may have detected radioactive tracer passing to the sequential nodes as well as that remaining in true sentinel nodes.

Type 2 segmental manifestation of disseminated superficial actinic porokeratosis in a 7-year-old girl.

We report here a rare case of porokeratosis in which two different clinical types of porokeratosis (linear porokeratosis and disseminated superficial actinic porokeratosis) coexisted. A 7-year-old girl developed a centrifugal lesion on her left abdomen at the age of 2, disseminated superficial actinic porokeratosis on her face at the age of 3 after ultraviolet exposure, and linear porokeratosis on her left body at the age of 5. Histological findings corresponded with cornoid lamella. She was treated with topical maxacalcitol ointment and cryotherapy with considerable improvement. The combination of different types of porokeratosis in one individual is rare. We consider that this case may represent a type 2 segmental manifestation of disseminated superficial actinic porokeratosis.

Increased expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and matrix metalloproteinase-13 in lesional skin of bullous pemphigoid.

BACKGROUND: Matrix metalloproteinase (MMP)-2, MMP-9 and MMP-13 can degrade type IV collagen which is the major component of the basement membrane zone (BMZ). In bullous pemphigoid (BP), the separation occurs within the BMZ. OBJECTIVE: To evaluate the involvement of MMPs in the pathogenesis of BP, we examined the expression of MMP-2, MMP-9 and MMP-13 in the lesional skin of BP patients. METHODS: The expression of MMP-2, MMP-9, MMP-13, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 was analyzed by immunohistochemistry in the lesional skin of BP patients in comparison with that in normal human skin. Next, the cellular sources of MMP-2, MMP-9 and MMP-13 were analyzed by double immunohistochemistry. Finally, the levels of these MMPs in the serum and blister fluid of BP patients were measured by ELISA. RESULTS: The number of cells expressing MMP-2, MMP-9 and MMP-13 were significantly increased in the lesional skin of BP patients as compared to that in normal skin. Although the number of cells expressing TIMP-1 and TIMP-2 were also increased in the lesional skin of BP patients as compared to that in normal skin, the ratio of MMPs to TIMPs in the lesional skin of BP patients was high (2.4:1). T cells comprised the major source of MMP-2, MMP-9 and MMP-13, while a proportion of mast cells and eosinophils also expressed these MMPs. Furthermore, marked expression of MMP-2 was detected in the epidermal keratinocytes. The levels of these MMPs in the blister fluid were significantly greater than those in the serum. CONCLUSION: These results suggest that MMP-2, MMP-9 and MMP-13 may be involved in the mechanism of blister formation in BP and that besides infiltrating inflammatory cells, structural cells like epidermal keratinocytes may also participate in the induction of blister formation in BP.

[The effect of suplatast tosilate on the patients with atopic dermatitis--relationship between clinical symptoms and immunological parameters].

The Th2 cytokine inhibitor, suplatast tosilate (300 mg/day) was administered to 45 cases of patients with atopic dermatitis for 8 weeks. The clinical scores, peripheral blood eosinophil counts, serum LDH levels, total IgE levels, serum eosinophil cationic protein (ECP) levels, and serum IL-5 levels before and after the treatment were observed and comparatively evaluated. The results of this study were summarized as follows. 1) Temporary improvements were found in the severity score, itching score, and sleeplessness score. All evaluated scores decreased significantly for all observation periods at 2, 4, 6 and 8 weeks after administration of suplatast tosilate compared with those before the administration. 2) In severe group, there was a significant improvement of severity score of lower limb. In moderate group there were significant improvements of severity score of head, face, neck and of upper limb. There were significant improvements of severity score of trunk and upper limbs in mild group. 3) The peripheral blood eosinophil counts and serum LDH levels significantly diminished compared with those before administration, but no significant difference was found in total IgE levels and serum ECP levels. 4) The serum IL-5 levels decreased after administration, however, there was no statistical significance. 5) The positive correlations between delta-severity score and delta-peripheral eosinophil count, delta-serum LDH levels, delta-serum ECP levels were found. 6) The positive correlations between delta-peripheral eosinophil count and delta-serum LDH levels, delta-serum ECP levels were observed. 7) There was no sign of adverse effects of the drug. From the above mentioned results, we confirmed the high efficacy of suplatast tosilate in the treatment of atopic dermatitis.

Paraneoplastic pemphigus associated with uterine carcinoma.

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease characterized by severe mucous membrane involvement, polymorphous skin eruptions, and underlying neoplasms, usually those of lymphoreticular system. Cases of PNP associated with solid cancer are extremely rare. A 46-year-old woman presented with severe stomatitis, pseudomembranous conjunctivitis, and polymorphous skin eruptions. Histologic, immunofluorescence, and immunoblot analyses confirmed the diagnosis of PNP. Whole-body examination revealed squamous cell carcinoma of the uterine cervix, but no hematologic tumors. Complete removal of the uterine tumor in addition to administration of betamethasone induced considerable improvement of cutaneous and mucous membrane lesions. To our knowledge, this is the first reported case of PNP associated with uterine carcinoma.

Mast cells in basal cell carcinoma express VEGF, IL-8 and RANTES.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignant tumor of the skin. Although an increase in mast cell infiltration was observed in BCC lesions, definite evidence of an active role of mast cells in the pathogenesis of BCC is still lacking. BCC is accompanied by cellular infiltrates. Moreover, the stroma in the BCC lesions is characterized by an increased number of mast cells and increased vascularity. The aim of this study was to elucidate the probable role of mast cells in BCC, especially focusing on the relationship between mast cells and lymphocytic infiltration as well as angiogenesis. METHODS: We examined the expression and distribution of VEGF, IL-8 and RANTES in 16 nodular BCC lesions by immunohistochemistry. We also examined the lymphocyte subset, and the correlation between VEGF expression and microvessel density in the BCC lesion. mRNA expression of IL-8 and RANTES was examined by the reverse transcriptase-polymerase chain reaction. RESULTS: T cells, especially CD4+/CD45RO+ memory T cells were the predominant infiltrating lymphocyte population in BCC lesions. An increased number of tryptase+ cells (mast cells) was found in the stroma. VEGF+/IL-8+/RANTES+ cells were also found abundantly in the stroma of all BCC lesions. The number of VEGF+, IL-8+ and RANTES+ cells was significantly higher than that in controls. By immunohistochemistry of serial sections, tryptase+ cells were found to express VEGF, IL-8 or RANTES. Messenger RNA expression of IL-8 and RANTES was also observed in the BCC lesions. CONCLUSION: This study suggests that mast cells may play an active role in the angiogenesis of BCC through the production of VEGF and IL-8. Furthermore, mast cells may also regulate lymphocytic infiltration through the production of IL-8 and RANTES.

Creeping eruption caused by a larva of the suborder Spirurina type X.

We report a case of creeping eruption caused by a larva of the suborder Spirurina type X, which developed in a 46-year-old Japanese male. The patient ate small raw squids (Watasenia scintillans) 5 days before the onset of symptoms. On examination, an approximately 25-cm-long serpiginous red track with vesicles was observed from the right to the upper left side of the abdomen of the patient. Histological examination revealed the transverse section of a larval worm in the upper to middle dermis.The patient serum was positive only for the antibody against larvae of the suborder Spirurina type X in ELISA, and negative for all other anti-parasite antibodies. Because a considerable number of people are fond of eating raw or nearly-raw fish and shellfish in Japan, opportunities for developing creeping eruption cause by parasites present in raw fish and shellfish are relatively high.

Desmoplastic trichoepithelioma: the association with compound nevus and ossification.

We report two cases of desmoplastic trichoepithelioma. One case was associated with compound nevus and the other case with ossification. Desmoplastic trichoepithelioma and nevus cell nevus are assumed to be a combined malformation. In our case 1, clinical and histological findings indicate that nevus cell nevus preceded desmoplastic trichoepithelioma and the latter developed in the lesion of the former. Ossification was reported to be associated with desmoplastic trichoepithelioma in 6% of cases. However, case reports of this combination with a detailed description are extremely rare. We speculate that the mechanism of ossification in this tumor must be related to foreign-body reactions caused by ruptured horn cysts.