Yuko Takenaka

Relationship between the severity of acne vulgaris and antimicrobial resistance of bacteria isolated from acne lesions in a hospital in Japan.

Propionibacterium acnes and Staphylococcus epidermidis are normal skin inhabitants that are frequently isolated from lesions caused by acne, and these micro-organisms are considered to contribute to the inflammation of acne. In the present study, we examined the antimicrobial susceptibilities and resistance mechanisms of P. acnes and S. epidermidis isolated from patients with acne vulgaris in a university hospital in Japan from 2009 to 2010. Additionally, we analysed the relationship between the antimicrobial resistance of P. acnes and the severity of acne vulgaris. Some P. acnes strains (18.8 %; 13/69) were resistant to clindamycin. All strains had a mutation in the 23S rRNA gene, except for one strain that expressed erm(X) encoding a 23S rRNA methylase. Tetracycline-resistant P. acnes strains were found to represent 4.3 % (3/69) of the strains, and this resistance was caused by a mutation in the 16S rRNA gene. Furthermore, three strains with reduced susceptibility to nadifloxacin (MIC = 16 µg ml(-1)) were detected. When analysing the correlation between the antimicrobial resistance of P. acnes and S. epidermidis, more than 80 % of the patients who carried clindamycin-resistant P. acnes also carried clindamycin-resistant S. epidermidis. However, no epidemic strain that exhibited antimicrobial resistance was detected in the P. acnes strains when analysed by PFGE. Therefore, our results suggest that the antimicrobial resistance of P. acnes is closely related to antimicrobial therapy. Additionally, those P. acnes strains tended to be frequently found in severe acne patients rather than in mild acne patients. Consequently, the data support a relationship between using antimicrobial agents and the emergence of antimicrobial resistance.

Glycolic acid chemical peeling improves inflammatory acne eruptions through its inhibitory and bactericidal effects on Propionibacterium acnes

Glycolic acid chemical peeling is effective for treating comedones, and some clinical data show that it also improves inflammatory eruptions. The purpose of this study was to identify the mechanism of glycolic acid chemical peeling to improve inflammatory acne. To assess growth inhibitory and bactericidal effects of glycolic acid on Propionibacterium acnes in vitro, we used an agar diffusion method and a time‐kill method. To reveal bactericidal effects in vivo, we established an agar‐attached method which correlated well with the ordinary swab‐wash method, and we used the agar‐attached method to compare the numbers of propionibacteria on the cheek treated with glycolic acid chemical peeling. Our results show that 30% glycolic acid (at pH 1.5, 3.5 and 5.5) formed growth inhibitory circles in the agar diffusion method, but the diameters of those circles were smaller than with 1% nadifloxacin lotion or 1% clindamycin gel. In the time‐kill method, 30% glycolic acid (at pH 1.5 and 3.5) or 1% nadifloxacin lotion reduced the number of P. acnes to less than 100 CFU/mL within 5 min. In contrast, in 30% glycolic acid (at pH 5.5) or in 1% clindamycin gel, P. acnes survived for more than 4 h. Chemical peeling with 35% glycolic acid (at pH 1.2) decreased the number of propionibacteria on the cheeks of patients compared with untreated controls (P < 0.01). Our results demonstrate that glycolic acid has moderate growth inhibitory and bactericidal effects on P. acnes, and that chemical peeling with glycolic acid works on inflammatory acne via those effects.

Propionibacterium acnes is developing gradual increase in resistance to oral tetracyclines

&NA; Propionibacterium acnes is an anaerobic bacterium that causes deep infection in organs and prosthetic joints, in addition to acne vulgaris. Many tetracycline‐resistant P. acnes strains have been isolated because oral tetracyclines are frequently used as an acne treatment against P. acnes. In this study, we found a novel tetracycline resistance mechanism in P. acnes. Three doxycycline‐resistant (MIC: 16 &mgr;g ml−1) strains were isolated from 69 strains in acne patients in Japan between 2010 and 2011. Additionally, six insusceptible strains (MIC: 1‐2 &mgr;g ml−1) that had reduced susceptibility compared to susceptible strains (MIC: ≤0.5 &mgr;g ml−1) were identified. All doxycycline‐resistant strains had a G1036C mutation in the 16S rRNA gene in addition to an amino acid substitution in the ribosomal S10 protein encoded by rpsJ. By contrast, insusceptible strains had an amino acid substitution in the S10 protein but no mutation in the 16S rRNA. When the mutant with decreased susceptibility to doxycycline was obtained in vitro, only the mutated S10 protein was found (MIC: 4 &mgr;g ml−1), not the mutated 16S rRNA gene. This result shows that the S10 protein amino acid substitution contributes to reduced doxycycline susceptibility in P. acnes and suggests that tetracycline resistance is acquired through a 16S rRNA mutation after the S10 protein amino acid substitution causes reduced susceptibility.

Paracrine cytokine mechanisms underlying the hyperpigmentation of seborrheic keratosis in covered skin areas

We previously reported that increased expression of the endothelin (EDN)1/EDNB receptor (EDNBR) as well as the stem cell factor (SCF)/SCF receptor (c‐KIT) linkages is mainly responsible for the activation of melanocytes in the epidermal hyperpigmentation of ultraviolet (UV)‐B melanosis and lentigo senilis (LS). In this study, we characterized seborrheic keratosis (SK) to examine the paracrine cytokine mechanism(s) involved in its epidermal hyperpigmentation by reverse transcription polymerase chain reaction, immunohistochemistry and western blotting analyses. In contrast to our previous study which showed the upregulated expression of EDN1 and EDNBR at the transcriptional and translational levels in the epidermis of SK, we observed unexpectedly that the cytokine SCF and its receptor c‐KIT are not upregulated, but are downregulated at both the gene and protein levels. We established SK cell lines to examine whether SK basaloid cells are less sensitive to SCF‐inducible stimulation than are normal human keratinocytes (NHK). Comparison of the stimulatory effects of interleukin (IL)‐1α or tumor necrosis factor (TNF)‐α on SCF production between SK cells and NHK demonstrated that SK cells do not respond to IL‐1α or TNF‐α to stimulate production of SCF, whereas a significant stimulation of SCF is elicited by those same cytokines in NHK. These finding underscore a role of phenotypic changes in melanogenic cytokine production in the epidermis between SK and LS/UV‐B melanosis.

Multiple basal cell carcinomas in an atomic bomb survivor

A 65-year-old woman with multiple skin nodules visited our hospital in 2008. In 1945, when she was 2 years old, she was exposed to atomic bomb radiation in Hiroshima. She developed thyroid and mammary cancer at the ages of 24 years and 46 years, respectively, and was treated by surgery and radiotherapy. At the age of 64 years, she noticed several nodules on her skin. When she visited our hospital, eight blackish or reddish nodules with diameters of £20 mm were present on her neck, lower back, left axilla and extremities (Fig. 1a–g). The patient showed no other symptoms of basal cell nevus syndrome (BCNS), including multiple odontogenic keratocysts in the mandible. Dermoscopy revealed arborizing vessels, multiple blue–gray globules or leaf-like areas on most of these nodules (Fig. 2). All the tumors were surgically removed. Histological examination revealed that the nodules comprised nests of basaloid cells in a palisading arrangement (Fig. 3); all these nodules were subsequently diagnosed as basal cell carcinoma (BCC). Two more BCCs, one on the thigh and the other on the hip, were discovered and removed during the 2-year follow-up period.

Case of acquired cutis laxa with preceding urticarial eruption treated by diphenyl sulfone

Dear Editor, A 35-year-old Chinese woman presented with a 9-month history of progressive loosening and wrinkling. For the preceding 3 years, she had suffered from urticarial eruptions which lasted several days, and were intractable to oral antihistamines. Physical examination revealed looseness and wrinkling of the eyelids, and around the mouth and chin (Fig. 1a). The earlobes were pendulous and loosened (Fig. 1b). Wrinkling with decreased elasticity was observed on the neck (Fig. 1c) and axillae (Fig. 1d). Edematous erythema without pruritus was observed on her arm (Fig. 1e) and abdomen. There was no hyperextensibility of the joints and fragility of the skin. Blood test and urine analysis were within the normal range. Chest X ray, chest and abdominal computed tomography, echocardiography and gastroscopy were normal. Histopathological examination from a urticarial eruption showed infiltrations of neutrophils around the blood vessels and between the collagen bundles (Fig. 1f). The histopathology of inelastic skin showed several clefts between the collagen bundles, and infiltrations of neutrophils and lymphocytes around the blood vessels. There was no infiltration of mast cells both in an urticarial eruption and in elastic skin. Elastica van Gieson staining revealed that the elastic fibers were sparse and shortened (Fig. 1g). In electron microscopy, several elastic fibers were present in each field under a 94000 magnification. We observed the adherence of one neutrophil to one fiber in almost all elastic fibers in each field (Fig. 1h). The length of the elastic fibers was less than normal. We diagnosed the patient with acquired cutis laxa (CL) with urticarial eruption. Treatment was initiated with diphenyl sulfone (DDS) to alleviate the urticarial eruption. There has been neither urticarial eruptions nor progress of loosening for 5 years under the treatment. Acquired CL is characterized by a reduced number and abnormal properties of elastic fiber. The disease affects the

Case of lichen planus induced by sitagliptin phosphate hydrate

Further careful examination of the patient did not uncover evidence of other lesions. The MTX was withdrawn and she was observed without additional resection or postoperative chemotherapy for more than 2 years with no evidence of recurrence or metastasis. Although plasma EBV DNA analysis has not been performed, she was diagnosed with primary cutaneous MTX-LPD from her clinical course with no recurrence after initial excisional biopsy. Methotrexate-associated lymphoproliferative disorder is a lymphoid proliferation or lymphoma arising in patients who are immunosuppressed by MTX therapy for treatment of an autoimmune disease, such as RA, psoriasis or dermatomyositis. Regarding its pathogenesis, an association with EBV infection is suspected and approximately 50% of cases are EBV positive. MTX-LPD can be either nodal or extranodal, and 21 cases of MTX-LPD with primary cutaneous lesion have been reported, including our case. Histologically, 80% of MTXLPD cases exhibit the features of diffuse large B-cell or follicular lymphomas and lesions with the features of HL account for 12%. Regarding primary cutaneous MTX-LPD, three cases showed features of HL, accounting for 14.3% (3/21) of all reported primary cutaneous MTX-LPD. While non-iatrogenic primary cutaneous HL is an extremely rare disease entity and its incidence is uncountable, there seems to be a higher incidence rate of primary cutaneous MTX-LPD showing HL features histologically. We speculate that immunosuppression of the cutaneous microenvironment by MTX more easily facilitates the evolution of precursor cells of HL into these extraordinary clinicopathological features. Additional studies should be done to elucidate its pathogenesis.