Treatment of giant congenital melanocytic nevi with cultured epithelial autografts: Clinical and histopathological analysis.

INTRODUCTION: Curettage and dermabrasion are effective in the treatment of giant congenital melanocytic nevi (GCMN); however, local infection and hypertrophic scar formation are major issues. Thus, we applied cultured epithelial autografts (CEA) on skin defects after curettage or abrasion of GCMN and assessed the postoperative outcomes. METHODS: Seven nevi lesions of five patients (aged 3 months to 24 years) were treated with CEA after curettage or abrasion with a dermatome or a surgical bar, respectively. We assessed the postoperative outcomes, including CEA take ratio, erosion and/or ulcer formation in the acute phase, hospitalization days, Vancouver scar scale, and color improvement one year after the operation. In addition, a histological evaluation of a skin biopsy was performed over one year after the operation. RESULTS: The CEAs took well on the wound, and the wound surface was mostly epithelized by postoperative day 7 in all cases. While hypertrophic scar formation and slight pigmentation were observed in some lesions, the color was improved in all of the treated lesions. Histopathological examination revealed that the regenerated epidermis had stratified keratinocytes with rete ridges, and the dermal layer without nevus cells regenerated above the remaining dermis layer. CONCLUSIONS: In this study, we found that early epithelialization and regeneration of the dermal layer was achieved after the application of CEA, suggesting that CEA could be an effective option after curettage or abrasion of GCMN.

Replantation of multi-level fingertip amputation using the pocket principle (palmar pocket method).

Two cases of multi-level fingertip amputation are presented. In each case, replantation was achieved in a two-stage procedure, involving reattachment, de-epithelialisation and insertion into a palmar pocket in stage 1, followed by removal from the palmar pocket 16 days later. The cases are described and the technique is discussed.

Amicrobial pustular dermatosis in two patients with immunological abnormalities.

We report two patients with severe amicrobial pustular dermatosis with immunological abnormalities: a 63-year-old woman with a 30-year-history of discoid lupus erythematosus and sicca syndrome, and a 35-year-old woman with high levels of gamma-globulinemia and positive antinuclear antibodies. Both patients presented with crusty and eroded erythematous plaques studded with aseptic pustules on the back, face, and scalp. Histological examination showed acanthosis, neutrophilic exocytosis to the epidermis, and neutrophilic and lymphocytic infiltration with nuclear dust in the dermis. These patients were diagnosed as having "amicrobial pustulosis associated with autoimmune diseases". The eruptions improved with combination treatment of oral prednisolone with cyclosporin A or diaminodiphenylsulphone. Although the pathogenesis remains unclear, amicrobial pustular dermatosis might be one of the cutaneous complications in autoimmune diseases.

Koebner phenomenon on skin graft donor site in cutaneous angiosarcoma.

An 81-year-old woman developed a necrotic plaque and a surrounding purple-red, irregularly shaped macule on her scalp. The diagnosis of angiosarcoma was confirmed histologically. A wide surgical excision was made followed by a split-thickness skin graft from her right buttock. Nine months later, she noticed a dark purple-red lesion on the donor site which grew rapidly into a large mass. Histological examination revealed irregular clefts and vascular channels lined by atypical endothelial cells. Lung metastasis and pneumothorax were also noted. The secondary tumor appeared to represent Koebner phenomenon in a patient with angiosarcoma of the scalp.

A combination of roxithromycin and imipenem as an antimicrobial strategy against biofilms formed by Staphylococcus aureus.

We examined the effects of a combination of roxithromycin and imipenem on a biofilm model of Staphylococcus aureus. Treatment with roxithromycin alone and imipenem alone did not decrease the number of viable bacterial cells compared with the control. However, a combination treatment of roxithromycin and imipenem significantly decreased the number of viable bacterial cells on day 8 after inoculation in the in vivo model (P < 0.01). On days 5 and 8 after inoculation, numerous polymorphonuclear leucocytes and macrophages invaded the bacterial clusters in the roxithromycin- and roxithromycin/imipenem-treated groups, but did not invade the control or imipenem-treated groups. The present study indicated that a combination of roxithromycin and imipenem is a potentially effective treatment for S. aureus biofilm-associated skin infections as it can induce the invasion of polymorphonuclear leucocytes into the biofilm.

Thyroid gland tumour, pemphigus foliaceus and myasthenia gravis in the daughter of a woman with myasthenia gravis.

We describe a rare case of pemphigus foliaceus associated with familial myasthenia gravis (MG). A 35-year-old woman developed MG during oral corticosteroid treatment for pemphigus foliaceus. She had been operated on for a thyroid gland tumour that was confirmed histopathologically to be papillary carcinoma without metastasis. At the time of treatment, her mother had had MG for 30 years and undergone thymectomy 22 years ago. A specific ELISA technique showed that antidesmoglein 1 antibody was present in the daughter. There are many reports of multiple diseases such as pemphigus, thymoma, malignancy, and other autoimmune diseases associated with MG. However, familial MG following pemphigus foliaceus has not been reported previously.

The palmar pocket method: an adjunct to the management of zone I and II fingertip amputations.

In 1979 Brent reported a new replantation method, without vascular anastomosis, that used a subcutaneous pocket. Brent chose the contralateral chest wall as a pocket site, but in other clinical reports, the abdominal wall was used. For both sites there were complications such as stiffness in the wrist, elbow, and shoulder joints and anxiety about pulling out the pocketed finger. To overcome these problems, we chose the ipsilateral palm and named this method the palmar pocket method. We used this method in 16 cases in which a digit other than the thumb had been amputated between the tip and lunula. In 13 cases the method was completely successful, and in 3 cases there was a small area of tip necrosis. The palmar pocket method is a simple and reliable operation for fingertip reattachment and more comfortable for patients than pocketing in the chest wall or abdominal wall.

Allergic contact dermatitis from a pyridine derivative in polyvinyl chloride leather.

Antimicrobial coating of household products has gained wide acceptance in Japan in the past several years. Pyridine derivatives, used as antifungal or antibacterial agents in many common products, are known to cause contact dermatitis. We present a case of severe contact dermatitis caused by a pyridine derivative used as an antifungal agent in the polyvinyl chloride (PVC) leather of a chair. An open patch test was performed with each ingredient of the PVC leather. Other products were previously eliminated from consideration based on a series of negative patch tests. The PVC leather obtained from the patient's chair gave a ++ reaction with evident blistering, according to the International Contact Dermatitis Research Group standard. Fifteen ingredients of the PVC leather were open patch tested; a positive reaction was found with 2,3,5,6-tetrachloro-4 (methylsulphonyl) pyridine (1% in petrolatum). Clinicians should be aware that antifungal or antibacterial agents may be increasingly incorporated into common household products and should be suspected in cases of contact dermatitis.

Numerical, morphological and phenotypic changes in Langerhans cells in the course of murine graft-versus-host disease.

BACKGROUND: In the course of graft-versus-host disease (GVHD) or diseases that histologically mimic GVHD (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome), it is known that epidermal Langerhans cells (LCs) are depleted from the epidermis. However, the mechanism and significance of LC depletion is not well known. OBJECTIVES: To investigate the numerical, morphological and phenotypic changes in LCs and apoptosis of LCs in the course of GVHD using a non-irradiated mouse GVHD model. METHODS: BALB/c nu/nu mice and C57BL/6 mice were used as recipients and donors, respectively. Recipient mice were injected with T-cell-enriched donor spleen cells. Skin samples were harvested at various times after the inoculation. The numerical and morphological changes were examined by an immunofluorescence study of epidermal sheets. Apoptosis was studied by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling method and flow cytometric analysis using annexin V. Phenotypic change was studied by flow cytometric analysis of epidermal cell suspensions. The mixed epidermal cell lymphocyte reaction (MELR) was performed to examine functional changes in the epidermal cells. RESULTS: Five days after inoculation, a graft-versus-host reaction occurred. Epidermal LCs began to decrease from the sixth day. On the fifth day, the LCs became larger and had prominent dendrites. Immediately before the LCs began to decrease, many LCs became round in shape, with scanty dendrites. LC apoptosis was not observed in the epidermis either on the fifth or seventh day. Phenotypically, the expression of CD40, CD80, CD86 and major histocompatibility complex class II antigen on the LCs was upregulated on the fifth and seventh day. Epidermal cells from GVHD mice showed an increased allostimulatory capacity in the secondary MELR. CONCLUSIONS: These results suggest that at early GVHD onset, most LCs may not undergo apoptosis in the epidermis but are phenotypically activated, resulting in further activation of alloreactive T cells and aggravation of the disease.

Antimicrobial effects of acidic hot-spring water on Staphylococcus aureus strains isolated from atopic dermatitis patients.

The present study examined the antimicrobial effects of acidic hot-spring water on Staphylococcus aureus strains isolated from atopic dermatitis (AD) patients. Plasma coagulation by S. aureus cells was not detected in plasma containing acidic hot-spring water (60%, pH 5.4) or hydrochloric acid (pH 5.0) after incubation for 24 h. S. aureus cells did not grow in Mueller-Hinton broth with acidic hot-spring water (50%, pH 4.4) after 24 h incubation. The colony counts of S. aureus cells in tryptic soy broth containing acidic hot-spring water (60%, pH 3.9) were over ten times lower than those in tryptic soy broth alone after incubation for 24 h (P<0.01). A membranous structure (an immature biofilm) was formed on the coverslips of tissue culture dishes by S. aureus cells in plasma after incubation for 24 h, although the colony counts of S. aureus cells in the immature biofilms in plasma containing acidic hot-spring water (60%, pH 5.4) were about eight times lower than those in plasma alone after incubation for 24 h (P<0.01). The colony counts of S. aureus cells that attached on coverslips in plasma containing acidic hot-spring water (60%, pH 5.4) or hydrochloric acid (pH 5.4) were over 1000 times lower than those in plasma alone after incubation for 24 h. These results suggest that 50% acidic hot-spring water has a bacteriostatic effect, 60% acidic hot-spring water has a moderate bactericidal effect against floating S. aureus cells and those cells in a biofilm, and, 60% acidic hot-spring water has an inhibitory effect on plasma coagulation and attachment of S. aureus cells. Furthermore, our present results suggest that a small amount of some ions in hot-spring water such as manganese and iodide ions are very important for a bactericidal activity of hot-spring water as well as the low pH condition.

The production of superantigenic exotoxins by coagulase-negative staphylococci isolated from human skin lesions.

We examined the production of superantigenic exotoxins in 136 coagulase-negative staphylococci isolated from various skin lesions in humans using a reversed passive latex agglutination test (Denka Seiken). As a control we examined the same in 50 Staphylococcus aureus strains isolated from non-infective skin ulcers in humans. Of the 136 strains of coagulase negative-staphylococci, 9 (6.6%) produced one or more identifiable exotoxins. In contrast, 21 (42%) out of the 50 S. aureus strains produced one or more identifiable exotoxins (P<0.01).

The brain link protein-1 (BRAL1): cDNA cloning, genomic structure, and characterization as a novel link protein expressed in adult brain.

We report here molecular cloning and expression analysis of the gene for a novel human brain link protein-1 (BRAL1) which is predominantly expressed in brain. The predicted open reading frame of human brain link protein-1 encoded a polypeptide of 340 amino acids containing three protein modules, the immunoglobulin-like fold and proteoglycan tandem repeat 1 and 2 domains, with an estimated mass of 38 kDa. The brain link protein-1 mRNA was exclusively present in brain. When analyzed during mouse development, it was detected solely in the adult brain. Concomitant expression pattern of mRNAs for brain link protein-1 and various lectican proteoglycans in brain suggests a possibility that brain link protein-1 functions to stabilize the binding between hyaluronan and brevican. The human BRAL1 gene contained 7 exons and spanned approximately 6 kb. The entire immunoglobulin-like fold was encoded by a single exon and the proteoglycan tandem repeat 1 and 2 domains were encoded by a single and two exons, respectively. The deduced amino acid sequence of human brain link protein-1 exhibited 45% identity with human cartilage link protein-1 (CRTL1), previously reported as link protein to stabilize aggregates of aggrecan and hyaluronan in cartilage. These results suggest that brain link protein-1 may have distinct function from cartilage link protein-1 and play specific roles, especially in the adult brain.

Adherence characteristics and susceptibility to antimicrobial agents of Staphylococcus aureus strains isolated from skin infections and atopic dermatitis.

We examined the adherence characteristics and susceptibility to various antimicrobial agents of 130 strains of Staphylococcus aureus isolated from infective skin lesions and 135 strains of S. aureus isolated from non-infective eczematous lesions of atopic dermatitis (AD) patients. The isolation rate of methicillin-resistant S. aureus (MRSA) was 27.7% in strains from clinical sources excluding AD and 31.1% in those from AD. Coagulase type II strains were most frequently observed in MRSA strains isolated from all sources excluding AD, and coagulase type III strains were most frequently observed in those isolated from AD. We proposed that antimicrobial treatment for AD patients should be carefully designed to prevent MRSA infection. Plasma coagulation ability was lowest in S. aureus strains isolated from abscesses, suggesting that the lower production of fibrin observed in abscesses may assist the infiltration of neutrophils into skin tissues and that a decrease in plasma coagulation ability may enable abscess formation. Adherence to polypropylene tubes with slime production was most evident in S. aureus strains isolated from felon and least evident in those isolated from cellulitis and lymphangitis. Tube adherence was characteristic of the S. aureus strains attached to superficial skin tissues, but not necessarily for strains that had infiltrated the deep skin tissues. Fusidic acid demonstrated significant antimicrobial activity against the MRSA strains, but rifampicin was the strongest antimicrobial agent.

Linear IgA disease with IgA antibodies directed against 200- and 280-kDa epidermal antigens.

We report an 80-year-old man with the lamina lucida type of linear IgA disease, with IgA autoantibodies reactive with 200-kDa and 280-kDa epidermal proteins. The patient presented with widespread bullous lesions on his trunk and extremities without mucosal involvement. Histopathology of lesional skin showed a subepidermal blister with papillary microabscesses of neutrophils and a few eosinophils. Direct immunofluorescence microscopy of perilesional skin showed linear deposits of IgA and C3 at the basement membrane zone. The patient's serum contained IgA autoantibodies that bound exclusively to the epidermal side of 1 mol L-1 NaCl split skin as determined by indirect immunofluorescence microscopy. Circulating IgA autoantibodies to 200- and 280-kDa antigens were detected in the patient's serum by immunoblot analysis using extracts from normal human epidermis and human epidermal keratinocytes. These two antibodies, eluted from individual nitrocellulose membranes, reacted with the epidermal side of 1 mol L-1 NaCl split skin on indirect immunofluorescence microscopy, and bound to hemidesmosomes as determined by immunoperoxidase electron microscopy. This observation suggests the presence of hitherto uncharacterized 200- and 280-kDa hemidesmosomal proteins distinct from BPAG1, BPAG2 and beta4 integrin as target antigens in linear IgA disease.

Palmoplantar pustulosis with pustulotic arthroosteitis involving temporal osteomyelitis and meningitis.

A 46-year-old man who had been suffering from palmoplantar pustulosis (PPP) for 3 years had anterior chest pain and left temporal pain from six months after the onset of his disease. A bone scan revealed abnormal uptake at the sternoclavicular joint and left temporal region. The head CT and MRI gave the diagnosis of temporal osteomyelitis with meningitis and myositis. His headache continued even after tonsillectomy and was effectively treated with cyclosporine A (3 mg/kg/day). Oral cyclosporine A was beneficial for the osteomyelitis and skin lesions. Sterile lytic bone lesions occurring most often at the sternocostoclavicular joint have been associated with PPP. However, there have been no reports of a PPP patient with temporal osteomyelytic involvement.

Expression pattern of the bcl-2 homologous protein bad in normal skin, psoriasis vulgaris and keratinocytic tumors.

Previous investigations focused on the mechanisms and regulation of apoptotic process have found that bcl-2 and its homologous proteins are central regulators of the mitochondrial phase of apoptosis. Expression of several members of the bcl-2 family has been studied in various tissues including skin under normal as well as disease conditions. In this report, we investigated the expression of bad, the pro-apoptotic member of the BH3 subfamily, in normal and psoriatic epidermis, keratoacanthoma, and basal and squamous cell carcinomas. Normal and psoriatic epidermis showed accentuation of the staining in the lower suprabasal compartment. A weak, predominantly diffuse staining pattern was observed in the upper epidermis of psoriatic plaques. Keratoacanthoma showed strong but diffuse immunostaining for pro-apoptotic bad, however we found only weak bad expression in squamous cell carcinoma. Seven out of 15 basal cell carcinomas failed to express bad protein. There was no correlation between bad positivity and depth of tumour infiltration. Our observation suggests that the pro-apoptotic bad may function as one of regulators involved in the maintenance of epidermal homeostasis and this function could be altered depending on the disease state.

[Azithromycin in the field of dermatology].

Azithromycin (AZM) is a new macrolides antibiotic that has a 15-membered ring structure obtained by introducing methyl-substituted nitrogen into a 14-membered ring lactone of erythromycin(EM). This article reviewed and summarized the clinical studies in the treatment of skin and skin structure infections conducted in Japan and abroad of AZM.