PTEN is a dual protein ; lipid phosphatase and hereditary heterozygous mutation of PTEN is associated in humans with Cowden disease, a rare autosomal dominant familial syndrome with a high risk of developing benign and malignant tumors in many organ systems. To investigate the role of PTEN in skin development and oncogenesis, we used the Cre-loxP system to generate a keratinocyte-specific null mutation of Pten in mice (k5Ptenflox/flox mice). k5Ptenflox/flox mice exhibit wrinkled skin as the result of epidermal hyperplasia and hyperkeratosis and ruffled, shaggy, and curly hair. Histological examination revealed that skin morphogenesis is accelerated in k5Ptenflox/flox mice. All k5Ptenflox/flox mice develop spontaneous tumors within 8.5 months of birth. PTEN is thus an essential regulator of normal homeostasis and oncogenesis in the skin.
The patient was a 28 year-old male diagnosed with recessive dystrophic epidermolysis bullosa with chronic ulcer formation on the dorsal area of the right hand (8 cm×4 cm in size) and right palm (5 cm×3.5 cm in size). The lesions have been intractable by conventional therapy for at least twelve months. This clinical study was designed to investigate the efficacy of allogeneic cultured dermal substitute (CDS) in the treatment of chronic skin ulcers of recessive dystrophic epidermolysis bullosa hereditaria. The wound conditions improved remarkably when treated with CDS for six weeks. The excellent clinical results obtained in this study suggest that the CDS can serve as a new cellular therapy for chronic skin ulcers in epidermolysis bullosa patients.
The prevalence of nasal carriers of community-acquired MRSA is becoming a clinical phenomenon of note in recent years, and, as if to reflect the social environmental context of the phenomenon, the number of reports on MRSA-related contagious impetigo and staphylococcal scalded skin syndrome (SSSS) has been increasing. Because the antibiotic susceptibility patterns of MRSA strains isolated from outpatients with acute infections, such as contagious impetigo and SSSS, often differ from those of MRSA strains isolated in nosocomial infections, we attempted to classify the MRSA strains isolated from outpatients by the in susceptibility pattern. We also assessed the isolated strains by the effects of antibiotics used in combination with fosfomycin (FOM). The MICs (μg/ml) against the MRSA isolates were determined for FOM alone and for CEZ, CTM, CMB, CFPM, SBT/ABPC, LVFX, MINO, ABK, IPM/CS, TEIC and VCM both individually and in combination with FOM. The 28 isolated strains of MRSA were classified into the following three groups by their patterns of susceptibility to MINO and FOM: Type A, strains highly susceptible to both MINO and FOM; Type B, strains highly susceptible to MINO but intermediately susceptible or resistant to FOM; and Type C, strains intermediately susceptible or resistant to both MINO and FOM. Type A and Type B strains were isolated in 6 and 10 cases, respectively. They were susceptible to all antibiotics tested, except for cephem and SBT/ABPC, and the number of cases by disease was largest for acute infection, such as contagious impetigo. When used in combination with FOM, the cephem and SBT/ABPC exhibited high susceptibility levels of MIC against Type A and Type B strains. Type C strains were isolated in 12 cases, and 8 of the 12 cases were observed in prolonged infections such as stasis dermatitis with secondary infection. The isolated strains were susceptible only to ABK, TEIC and VCM; however, LVFX exhibited susceptibility levels of MIC when used in combination with FOM. It was suggested that a long-term administration of antibiotics resulted in resolution of infection by bacteria except for Type C strains of high drug resistance or resulted in letting Type C strains select the high drug resistance, or Type C strains isolated as nosocomial infections during the long-term therapy at outpatient. On the other hand, the acute infections due to Type C strains observed in 4 cases were considered to be community-acquired infections, as were possibly the cases with Type A strain- and Type B strain-related acute infections. These results concern about the prevalence of nasal carriers of Type C strains of high drug resistance in community. In the present study, we demonstrated that the level of synergistic effect in combination with FOM can be predicted for each antibiotic agent based on the pattern of susceptibility of the isolated MRSA strains to each agent, and the predict was thought to be applied to the patients with MRSA infection not only of the skin or the upper respiratory tract but also of the internal organs such as pneumonia. The results of the present study also suggested that infection with Type B strains can be sufficiently treated by the combined use of either the first generation or second generation cephem and FOM without the use of broad spectrum antibiotics or antibiotics fraught with risks of serious adverse reactions, while more aggressive antibiotic therapy using FOM with ABK, TEIC or VCM was considered necessary for relatively more severe cases (even in cases of SSSS) of infection with Type C strains. Since LVFX, which is not indicated for pediatric use, became effective against Type C strains when used in combination with FOM, the combination therapy with FOM and new quinolone was considered useful in adult patients.
We examined 77 HE stained biopsy specimens of prurigo chronica multiformis Lutz histopathologically. Prurigo chronica multiformis Lutz is characterized as a chronic lesion of unknown origin and is characterized by the complex of erythema, wheal, papules, nodules, lichenification, and scratched scars chiefly on the side of the trunk, buttocks, thighs, and upper arms with severe itching, and favors middle-aged and elderly men. The histopathological diagnoses of the 77 cases were as follows: 52 cases of arthropod reaction, 15 cases of urticarial reaction, 6 cases of spongiotic dermatitis, and 1 case each of interface dermatitis-vacuolar type, lichen simplex chronicus, pseudolymphoma and superficial type of scar. We concluded that arthropod reaction is the most common histopathological finding of prurigo chronica multiformis Lutz.
We report a 66-year-old man with Sézary syndrome (SzS) treated with natural interferon-gamma (nIFN-γ). He first visited our hospital on August 30, 1999, complaining of pruritic erythema on his trunk. Although the topical therapy with steroids was continued, he presented with gradually increasing generalized erythroderma. On physical examination, enlarged lymph nodes were palpable in his neck, axilla, and groin. Biopsy specimens of the left groin lymph nodes showed dermatopathic lymphadenitis, but the skin specimen revealed dense upper dermal band-like infiltration composed of atypical lymphocytes. The white blood cell count was 17,700/μl with 21.5% atypical lymphoid cells with prominent nuclear convolutions and infoldings typical of Sézary cells. The DNA gene rearrangement study of the peripheral blood showed identical clonal rearrangements of the TCR βchain gene. We diagnosed him as SzS. The combination therapy of prednisolone and nIFN-γ was very effective, and the patient responded clinically with complete clearance of his skin and disappearance of the lymphadenopathy. There were no severe side effects during treatment. The patient currently remains in complete clinical remission about one year since his diagnosis.
Reflex sympathetic dystrophy (RSD), recently recategorized as complex regional pain syndrome type 1, is a poorly understood syndrome that consists of multiple symptoms, including chronic severe pain or allodynia/hyperalgesia, vasomotor instability, swelling, and bone dystrophy. We present two cases of RSD. The first case is a 54-year-old woman with chronic severe pain, swelling, and bone atrophy that appeared one month after the operation for granuloma telangiectaticum on the tip of the second finger of the left hand. The second case is a 32-year-old woman who presented at our department with redness, swelling, and severe pain of the right toe. The use of physiotherapy and beraprost sodium (PGI2) for Case 1 and sympathetic blocks for Case 2 resulted in progressive improvement of the disease, which healed with tolerable pain within a year. Although we dermatologists rarely encounter patients with RSD, it is highly important to recognize this disease entity for early diagnosis and early treatment.
Bullous pemphgoid (BP) is an acquired autoimmune subepidermal blisterng disease, which shows various symptoms, including bulla, polymorphic erythema, and pruritus. There is often an eosinophilia and raised serum IgE. The target antigens are hemidesmosomal cytoplasmic BP230 and transmembrane BP180 proteins. In this study, we investigated the correlation among the clinical symptoms, serum IgE, the eosinophil count, indirect immunofluorescence titer, and BP180NC16a scores measured by enzyme-linked immunosorbent assay (ELISA). With clinical improvement, all of these values decrease ; the BP180NC16a scores and the eosinophil count were particularly closely correlated. At the disease relapsed, the BP180NC16a score was the most sensitive indicator. In patients exhibiting high levels of BP180NC16a scores greater than 150 by regular ELISA, we again performed ELISA with appropriate dilutions and obtained true index values that exhibited a better correlation with disease activity. During plasma exchange, we could detect the reduction of the pathogenic anti-BP180NC16a autoantibody by using ELISA. These findings indicate that BP180NC16a ELISA can be valuable not only for the diagnosis of patients with BP but also for monitoring disease activity.