International expert consensus recommendations for the use of dermocosmetics in acne.

BACKGROUND: A wide variety of dermocosmetics (products with both active skincare and cosmetic activity) are available for the management of acne vulgaris. These products are important because they may be the first line of approach for patients desiring to self-treat and they can also have beneficial effects-reducing lesion counts and improving global acne severity. When used in conjunction with medical therapy, dermocosmetics can improve tolerability and enhance results. We reviewed available evidence and combined it with our clinical experience to help guide clinicians in selecting skincare products with acne-targeting ingredients. METHODS: An international panel of dermatologists with an interest and expertise in managing acne performed a literature review, formulated clinical questions related to the role of dermocosmetics in the acne setting, used a modified GRADE approach to evaluate available evidence and then utilized an online iterative Delphi process to create consensus recommendations. It should be noted that due to the limited number of available studies, the category of dermocosmetics was evaluated rather than specific ingredients. RESULTS: The quality of evidence was found to be low to moderate. Key recommendations were made based on available evidence for the use of dermocosmetics in acne to improve acne global assessment, reduce acne lesion counts, reduce superficial skin oiliness and serve as maintenance therapy after medical treatment, while providing a good tolerability. Recommendations were also made for using dermocosmetics as adjuncts to medical treatment. CONCLUSIONS: While there is a need for better quality evidence, dermocosmetics have demonstrated some benefit for acne both when used alone in its milder clinical presentations or in maintenance post acne medication and as adjunct to acne treatments.

Antimicrobial activity of ozenoxacin and other antimicrobials against Staphylococcus aureus strains isolated from clinical skin specimens in Japan in 2019 and 2020.

Skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and the spread of antimicrobial resistance are a major problem in Japan. Here, we investigated the susceptibility of S. aureus clinical isolates to ozenoxacin (OZNX), a topical antimicrobial approved for superficial skin infection treatment in Japan. Susceptibility to OZNX was measured in 110 skin-derived methicillin-susceptible S. aureus (MSSA) and 130 MRSA strains isolated in 2019 and 2020 in Japan. The broth microdilution method was performed, and results were analyzed according to the Clinical and Laboratory Standard Institute (M07 and M100) guidelines. The results were compared with those of other antimicrobials used against S. aureus. The minimum inhibitory concentrations (MIC)90 of OZNX for MSSA and MRSA were 0.12 and 0.25 µg/mL, respectively, indicating that OZNX exhibited the same or stronger antibacterial activity than that of the other antimicrobials tested, such as nadifloxacin, fucidic acid, and gentamicin. No strains exhibited reduced OZNX susceptibility. Notably, a low MIC of OZNX was observed even for strains with reduced susceptibility to nadifloxacin, a similar quinolone-based topical antimicrobial. OZNX is a highly potent antimicrobial used in Japan for superficial skin infections caused by S. aureus, such as impetigo contagiosa and related diseases.

Hidradenitis suppurativa in South-East Asia and East Asia.

Hidradenitis suppurativa (HS) in South-East Asia and East Asia shows distinct clinical, environmental, physiological and likely genetic differences compared with the West. A male predominance is present, which may be due to differences in smoking habits. Involvement of the buttocks is common in East Asian patients, while the axillae are most commonly affected in South-East Asian patients. Metabolic comorbidities are prevalent in South-East Asian and East Asian HS patients. A family history of HS is less common than noted in Western populations. Asian ethnic subgroups deserve further study.

The first nationwide surveillance of antibacterial susceptibility patterns of pathogens isolated from skin and soft-tissue infections in dermatology departments in Japan.

To investigate the trends of antimicrobial resistance in pathogens isolated from skin and soft-tissue infections (SSTI) at dermatology departments in Japan, a Japanese surveillance committee conducted the first nationwide survey in 2013. Three main organisms were collected from SSTI at 30 dermatology departments in medical centers and 10 dermatology clinics. A total of 860 strains - 579 of Staphylococcus aureus, 240 of coagulase-negative Staphylococci, and 41 of Streptococcus pyogenes - were collected and shipped to a central laboratory for antimicrobial susceptibility testing. The patient profiles were also studied. Among all 579 strains of S. aureus, 141 (24.4%) were methicillin-resistant (MRSA). Among 97 Staphylococcus epidermidis strains, 54 (55.7%) were methicillin-resistant (MRSE). MRSA and MRSE were more frequently isolated from inpatients than from outpatients. Furthermore, these methicillin-resistant strains were also isolated more frequently from patients with histories of taking antibiotics within 4 weeks and hospitalization within 1 year compared to those without. However, there were no significant differences in MIC values and susceptibility patterns of the MRSA strains between patients with a history of hospitalization within 1 year and those without. Therefore, most of the isolated MRSA cases at dermatology departments are not healthcare-acquired, but community-acquired MRSA. S. pyogenes strains were susceptible to most antibiotics except macrolides. The information in this study is not only important in terms of local public health but will also contribute to an understanding of epidemic clones of pathogens from SSTI.

Beyond acne: Current aspects of sebaceous gland biology and function.

The sebaceous gland is most commonly found in association with a hair follicle. Its traditional function is the holocrine production of sebum, a complex mixture of lipids, cell debris, and other rather poorly characterized substances. Due to the gland's central role in acne pathogenesis, early research had focused on its lipogenic activity. Less studied aspects of the sebaceous gland, such as stem cell biology, the regulation of cellular differentiation by transcription factors, the significance of specific lipid fractions, the endocrine and specially the neuroendocrine role of the sebaceous gland, and its contribution to the innate immunity, the detoxification of the skin, and skin aging have only recently attracted the attention of researchers from different disciplines. Here, we summarize recent multidisciplinary progress in sebaceous gland research and discuss how sebaceous gland research may stimulate the development of novel therapeutic strategies targeting specific molecular pathways of the pathogenesis of skin diseases.

Successful treatment of ulceration in hidradenitis suppurativa with topical bucladesine: A case report.

We report a case of hidradenitis suppurativa (HS) with skin ulceration in a 19-year-old man. He was successfully treated with topical bucladesine ointment treatment, resulting in a hypertrophic scar 2 months after the treatment. Bucladesine can be an alternative treatment option for ulceration in HS.

What is the role of antimicrobial peptides (AMP) in acne vulgaris?

Acne vulgaris is the most common disorder of the pilosebaceous unit leading to inflamed skin characterized by the formation of comedones, papules, pustules and scarring. There is increasing evidence that the abundance of Propionibacterium acnes (P. acnes) in the inflamed acne lesions triggers inflammation. Therefore, in addition to treatment with retinoids, the use of antimicrobial agents has been established as a treatment option for acne. This indicates that antimicrobial mechanisms to control the growth of P. acnes may have an important influence on the severity of inflammatory acne. One import antimicrobial innate defense system comprises the production of antimicrobial peptides (AMP), small molecules with a broad spectrum of antimicrobial activity as well as immunomodulatory properties. Although the role of AMP in acne is still emerging, there is increasing evidence that AMP may be of importance in acne. The aim of this viewpoint is to provide some hypotheses about the potential function of AMP in the pathogenesis of acne and to discuss potential AMP-based therapies for the treatment of acne.

Early diagnosis of Japan spotted fever by PCR using skin samples.

We studied the suitability of a PCR method using samples of skin and whole blood and serological tests for the early diagnosis of Japan spotted fever (JSF) in its acute and convalescent stages and compared the advantages and disadvantages of these different diagnostic methods. In the acute stage, the percentage of positive results was 91.2 % for the PCR method using skin samples, 52.3 % for the PCR method using whole blood samples, and 40.4 % for the serological tests with IgM. In the convalescent stage, paired serum showed positive results (IgM, 98.5 %; IgG, 94.0 %). [corrected]. The PCR method using samples of skin (eschar) is the most sensitive, specific, and suitable method for promptly and accurately diagnosing JSF in the early stage. Therefore, this method is recommended for early definite diagnosis of JSF in the critical stage.

The Role and Benefits of Dermocosmetics in Acne Management in Japan.

In Japan, as in other countries around the world, acne vulgaris is a common disease and a frequent reason for patients to consult dermatologists. For optimal management of acne, it is important to understand how available products to support skin health can be used both with and without prescription products. Dermocosmetics can be defined as skincare agents with dermatologically active ingredients that directly support or care for the symptoms of various skin conditions (distinct from vehicle effects). There are products with active ingredients-including familiar ones such as niacinamide, retinol derivatives, and salicylic acid-that target important aspects of acne pathophysiology. Others, including ceramides, glyercin, thermal spring water, and panthenols, may have positive effects on skin barrier function that are useful in managing acne. This publication will discuss the roles of dermocosmetics in acne either as monotherapy to manage the milder forms of acne and help prevent relapses, or as adjuncts to prescription therapy to increase efficacy or adherence and assist in prevention of local adverse effects. Dermocosmetics may also have active ingredients that positively impact the skin microbiome.

Real-world safety and effectiveness of adalimumab in patients with hidradenitis suppurativa: A 52-week analysis of a postmarketing surveillance study in Japan.

Adalimumab is a human monoclonal antibody against tumor necrosis factor-α that was approved in Japan for the treatment of hidradenitis suppurativa (HS), a chronic recurrent inflammatory skin disease. We report the results of the final analysis of the postmarketing surveillance (PMS) study (ClinicalTrials.gov: NCT03894956), which evaluated the 52-week safety and efficacy of adalimumab for HS treatment in real-world clinical practice in Japan. This multicenter, prospective, open-label, observational study (March 2019 to May 2021) included patients with HS treated with subcutaneous adalimumab at doses following the package insert. The primary endpoint was safety, and the secondary endpoints were effectiveness, including HS clinical response (HiSCR), C-reactive protein (CRP), skin pain, and Dermatology Life Quality Index (DLQI). Of the 84 patients registered at 65 sites, 83 patients were included in the analyses. Adverse drug reactions (ADRs) were reported by 10 (12.0%) patients; two patients reported a serious ADR, including one patient with serious infection. Other safety events of special interest reported were liver disorder and dermatitis psoriasiform (one patient each). Almost all patients with ADRs were recovering or had recovered, except for one patient who experienced a serious ADR of liver disorder and died. At 12 weeks, 55.4% of patients achieved HiSCR; this increased to 60.5% and 62.8% at 24 and 52 weeks of adalimumab treatment, respectively. Significant reductions from baseline in CRP (P < 0.05), skin pain (P < 0.0001), and DLQI (P < 0.0001) were observed at all time points. The results from this PMS study demonstrated that long-term adalimumab treatment is well tolerated and effective in patients with HS in real-world clinical practice in Japan.

Prurigo pigmentosa clinically and immunologically mimicking autoimmune bullous disease: A case report.

A 15-year-old Japanese male noticed brown macules on his back 9 months ago. Initial examination revealed reticulated infiltrative erythema and pigmentation with blisters on the erythema of the back. Histopathology showed blisters with eosinophil infiltration in the epidermis, and direct immunofluorescence showed negative results for immunoglobulin (Ig) G, Ig A, Ig M, and C3 in the epidermal basement membrane zone. Immuno-serological tests revealed the presence of IgG antibodies against BP180, linear IgA disease antigen 1 (LAD-1), and laminin α3. The autoimmune bullous disease was suspected, and prednisolone at a concentration of 20 mg/day (0.3 mg/kg/day) was started. When the prednisolone dose was reduced to 10 mg/day, erythema and blisters recurred. The patient was diagnosed with prurigo pigmentosa based on clinical features and was treated successfully with oral doxycycline hydrochloride hydrate and topical tacrolimus ointment. This is the first case of prurigo pigmentosa with blisters in which autoantibodies to the epidermal basement membrane zone were found, which might be secondary non-pathogenic antibodies.

Real-world safety and effectiveness of adalimumab in patients with hidradenitis suppurativa: 12-week interim analysis of post-marketing surveillance in Japan.

Hidradenitis suppurativa (HS) is a painful chronic skin disease characterized by abscesses, nodules, and tunnels in the skin. Adalimumab, a monoclonal antibody against tumor necrosis factor-α, is approved for the treatment of HS in Europe, the USA, and Japan. This multicenter, open-label, post-marketing, observational study (ClinicalTrials.gov: NCT03894956) evaluated the safety and effectiveness of adalimumab in routine clinical practice in Japan (March 2019-May 2021). Patients with HS were treated with s.c. doses of adalimumab according to the dosage described in the package insert. The primary end-point was safety (data cut-off, December 2020). Secondary end-points assessed effectiveness, including HS Clinical Response (HiSCR), skin pain, Dermatology Life Quality Index (DLQI), and C-reactive protein (CRP). Here, we report 12-week interim effectiveness results. A total of 84 eligible patients from 65 sites were enrolled; 83 patients were included in this analysis. Mean age was 42.0 years, mean body mass index was 26.9 kg/m2 , 78.3% of patients were male, 61.4% had Hurley stage III disease, 39.8% had a disease duration ≥10 years, and 7.2% had a family history of HS. The most common affected sites were the axilla (60.2%), buttocks (59.0%), and the inguinal and femoral regions (47.0%). Mean abscess and inflammatory nodule count was 13.0 (standard deviation, 12.0). Among patients with a comorbidity (57.8%), the most common were diabetes mellitus, hypertension, and chronic kidney disease. No patient reported a serious infection or any safety event of special interest. One patient died from a serious adverse event of cardiac failure unrelated to adalimumab. At week 12, 57.4% of patients achieved HiSCR, and significant reductions from baseline in skin pain, DLQI (both p < 0.0001), and CRP (p = 0.0029) were observed. These results support the administration of adalimumab as a well-tolerated and effective treatment for Japanese patients with HS in real-world clinical practice.

Expression of keratins in cutaneous epithelial tumors and related disorders--distribution and clinical significance.

Keratins are a highly diverse family of cytoskeletal proteins and important markers of epithelial cell differentiation. In this review, applying the new keratin nomenclature recently introduced, we summarize and discuss the distribution and significance of keratin patterns in cutaneous epithelial tumors in relation to the epithelial structures of normal human skin. The available literature data show that the analysis of keratin profiles broadens our understanding of the differentiation, nature and histogenetic origin of the various, highly singular epithelial tumors arising in the skin. Moreover, keratins may aid in histological diagnosis and, in certain instances, may be helpful for the recognition of tumor malignancy and aggressiveness. Furthermore, we briefly address the topic of keratin-related skin disorders.

Propionibacterium acnes vaccination induces regulatory T cells and Th1 immune responses and improves mouse atopic dermatitis.

Atopic dermatitis (AD) is a chronic disease characterized by a polarized Th2 immune response. Propionibacterium acnes (P. acnes) has been shown to elicit strong Th1 immune responses. We hypothesized that the host immune response to P. acnes will prevent the development of AD. To demonstrate this hypothesis, we investigated the effect of P. acnes vaccination on AD that occurs in keratin 14/driven caspase-1 transgenic mouse. Vaccination with low dose of P. acnes successfully prevented clinical manifestations in the skin of AD mice associated with systemic and cutaneous increased expression of Th1-type cytokines but without suppression of Th2 cytokines. Interestingly, the numbers of IFN-γ(+) T cells, FoxP3(+) CD4(+) CD25(+) T cells (nTreg) and IL-10(+) T cells (Tr1) were significantly increased in the spleen. P. acnes vaccination has effects to alter the cytokine milieu and may be useful for the improvement of atopic symptom.

The histopathological feature of the nail isthmus in an ectopic nail.

The nail unit has a unique structure. It has been recently proposed that the nail isthmus as a transitional zone between the most distal part of the nail bed and the hyponychium. A 7-year-old Japanese boy presented with an ectopic nail, an additional and independent miniature nail on the digital pulp of the right fifth finger. We studied the expression of a series of keratin in longitudinal specimens and showed the histopathological manifestation in the nail isthmus. This region in the ectopic nail is subdivided into 2 parts: a proximal and narrow part anchored to the nail plate and a distal and wide part with a semihard keratinized structure.

SLIT improves cedar pollinosis by restoring IL-10 production from Tr1 and Monocytes∼IL-10 productivity is critical for becoming allergic∼.

BACKGROUND: Allergen-specific immunotherapy (SIT) is currently used for several allergic disorders and IL-10-producing regulatory T cells (Tr1) induced by SIT suppress allergic reactions. We investigated the relation between IL-10 production and acquiring allergy. METHODS: A prospective study was undertaken to evaluate the effect of SIT on IL-10 production in T cells and other cell fractions in children with pollinosis. In addition, blood samples were collected from non-allergic healthy controls and patients with pollinosis to compare the levels of IL-10 production. PBMC were cultured with pollen peptides or control allergens, and the IL-10 production from monocyte and CD4 T cell was analyzed. RESULTS: Monocytes and CD4 T cells from SIT group of patients produced high levels of IL-10, suggesting that the induction of IL-10 is essential for inducing T cell tolerance. IL-10 production from monocytes and T cells was significantly increased in non-allergic controls compared to patients with pollinosis. This high IL-10 production was observed even when PBMC were stimulated with antigens other than pollen peptides. CONCLUSIONS: IL-10 is critical for induction of specific T cell tolerance, and increased production of IL-10 by monocytes and T cells during inflammatory responses or after SIT may influence effector cells in allergy. Present data implicates that the low productivity of IL-10 by monocytes and T cells is closely related with sensitivity to multiple allergens, and resistance to allergic diseases. Augmentation of constitutive IL-10 production from immune system is a potential therapeutic approach for allergic disorders.

Updated Treatment for Acne: Targeted Therapy Based on Pathogenesis.

Previous approaches to acne management have focused on the four main factors implicated in acne, namely, androgen-mediated sebogenesis (considered integral to acne), hyperkeratinization, colonization with Cutibacterium acnes, and inflammation related to both innate and adaptive mechanisms. Recent advances have facilitated potential novel approaches to acne management, as the pathophysiology and the immunological aspects related to acne and wound healing have evolved. Particular targets that have been shown to be closely involved in acne pathophysiology and wound healing include interleukin (IL)-1ß, IL-17, IL-23, and tumor necrosis factor alpha (TNFα). Biological antibodies targeting IL-1ß, IL-17, IL-23, and TNFα could provide novel approaches for treating severe acne and related disorders. Acne is primarily a disease associated with sebogenesis. Monosaturated free acids are important components. Insulin growth factor 1 (IGF-1) promotes the proliferation and differentiation of sebocytes and IL-1ß. Research into the microbiome may also provide insights into potential future therapeutic options for acne. Scars, both atrophic and hypertrophic, are common sequelae to acne. Risk factors associated with the development of acne scars include genetic, systemic, local, and lifestyle factors. Pro-inflammatory cytokines have been shown to play a crucial role in the development of acne-induced hypertrophic scars. Treatment for extensive inflammatory keloid scarring is limited. Surgery and postoperative radiotherapy are two possible options. Transforming growth factor-ß (TGFß), IL-6, matrix metalloproteinase (MMP), IGF-1, and B cells are found in keloid or hypertrophic scar tissues. Biological antibodies targeting these cytokines may be a potential strategy for the prevention and treatment of this type of scar in the future. Future treatment for acne should embrace approaches that target the main etiological factors of acne. In particular, specific emphasis on aggressive treatment in the acute inflammatory phase to reduce the likelihood of scarring and other clinical sequelae, such as pigmentary changes would be highly desirable. Treatment for established acne-induced sequelae should also be considered.

Letter: Adult measles with a butterfly rash-like appearance.

Butterfly rash is characterized by symmetrical erythema and erythematous papules and plaques grouped on the bilateral cheeks and nose, commonly found in lupus erythematosus. Measles is a highly contagious viral disease, characterized by high fever, cough, coryza, conjunctivitis, and Koplik spots, which precede generalized maculo-papular rashes. We report an adult case of measles, accompanied by butterfly rash. A 20-year-old woman came to our hospital with a butterfly rash-like eruption on the face, high fever, and arthralgia. The eruption had appeared on the nose and both cheeks three days before admission. The oral mucosa was not involved. On the basis of the three criteria for a diagnosis of lupus eruthematosus, we first made a tentative diagnosis of lupus eruthematosus and performed blood tests. However, anti-DNA antibodies, scl-70, anti-Ro and La, anti-Sm and rheumatoid factor were all negative. Two days after admission, a Koplik macule appeared along with multiple erythematous macules and papules that were scattered through the trunk. Laboratory tests were positive for anti-measles immunoglobulin M and G. Therefore, we reached a diagnosis of measles. Within a week, all of the clinical symptoms disappeared. Physicians should be aware that, in rare cases, measles may present with a butterfly-like rash.

Recent advances in understanding and managing acne.

Multidisciplinary investigations into the pathogenesis of acne have significantly progressed over the past three years. Studies of the etiology of acne from the perspectives, for example, of sebaceous gland biology, sebum, genetics, keratinization, differentiation, hair cycles, immunology, bacteriology, and wound healing have elucidated its pathogenesis. This has led to the development of new therapies and paved the way for advanced studies that will enable the further evolution of acne treatment.