Real-world safety and efficacy of biologics in elderly patients with psoriasis: A multicenter observational study.

Clinical trials of biologics have frequently excluded elderly patients, resulting in inadequate data on their safety and efficacy. Additionally, evidence of their safety and efficacy remains limited, despite some real-world studies. To assess the safety and efficacy of biologics in elderly patients with psoriasis, we compared these outcomes in younger patients using data from the West Japan Psoriasis Registry (WJPR). The WJPR consists of approximately 30 facilities in Western Japan, including various healthcare settings. This study enrolled 1395 patients who participated in the 2022 follow-up survey of the WJPR and were either using or had used biologics during the survey. These included 456 patients in the elderly group (≥65 years) and 939 patients in the younger group (<65 years). Treatment-ending adverse events (TEAEs) occurred in 15.8% and 11.3% of elderly and younger patients, respectively. The incidence rate per 1000 patient-years (PY) for TEAEs was significantly higher in elderly patients than in younger patients (32.9 vs 23.2, p = 0.0234). Infectious diseases were more prevalent in the elderly group than the younger group; however, no significant difference in the frequency of infectious diseases was found between the two groups (p = 0.0807). Malignant neoplasms occurred significantly more frequently in the elderly group than in the younger group (p = 0.0169). Our results indicate a few concerns about infection when prescribing biologics to elderly patients. Biologics were effective for both elderly and younger patients. We found no significant differences in the proportion of patients with a body surface area score ≤3%, Physician's Global Assessment score 0/1, or Patient's Global Assessment score 0/1, as well as in the mean Dermatology Life Quality Index and the Itch Numerical Rating Scale between the younger and the elderly groups. Overall, our results confirm the appropriateness of using biologics in elderly patients with regard to safety and efficacy.

Thick Skin on the Dorsal Spine in Osteoproliferative Disease: Ossification of the Posterior Longitudinal Ligament and Diffuse Idiopathic Skeletal Hyperostosis.

Background Although the correlation between reduced skin thickness and reduced bone density has been investigated, no study has evaluated skin thickness and osteoproliferative diseases, including ossification of the posterior longitudinal ligament (OPLL) and diffuse idiopathic skeletal hyperostosis (DISH). Methodology This retrospective cohort study consisted of 99 consecutive patients aged ≥60 years treated for spinal surgery at our hospital between January 2022 and March 2023. Skin thickness was measured at the dorsal side of the cervical, thoracic, and lumbar vertebrae on the sagittal cross-section image of whole-spine CT. Based on the median value, skin thickness was categorized into two groups based on a median thickness of 4 mm. Bone mineral density (BMD) was assessed. The sum of the vertebral body and intervertebral bridging osteophytes of the anterior longitudinal and posterior longitudinal ligament were defined as the OALL index and OPLL index. Serum levels of bone metabolism-related markers, such as tartrate-resistant acid phosphatase type 5b, procollagen I N-propeptide, 25-hydroxyvitamin D, and periostin, were measured. To assess the association between skin thickness and imaging findings, we calculated the adjusted odds ratios, adjusting for age, sex, and body mass index (BMI) and using univariate and multivariate logistic regression analyses. Results No significant differences were found in skin thickness in the three dorsal regions of the cervical, thoracic, and lumbar spine (median = 3.3 mm versus 3.5 mm versus 3.4 mm, p = 0.357) and bone metabolism-related markers. Adjusting for age, sex, and BMI, cervical, thoracic, and lumbar skin thicknesses were related to DISH, the OPLL index, and the OPLL and OPLL index, respectively. Conclusions Skin thickness did not correlate with BMD but with the amount of spinal ossification. A correlation was found between skin thickness and vertebral and intervertebral ossification; vertebral osteophytes, OPLL, and DISH may be more common in thicker skin.

A view on the skin-bone axis: unraveling similarities and potential of crosstalk.

The phrase "skin as a mirror of internal medicine," which means that the skin reflects many of the diseases of the internal organs, is a well-known notion. Despite the phenotypic differences between the soft skin and hard bone, the skin and bone are highly associated. Skin and bone consist of fibroblasts and osteoblasts, respectively, which secrete collagen and are involved in synthesis, while Langerhans cells and osteoclasts control turnover. Moreover, the quality and quantity of collagen in the skin and bone may be modified by aging, inflammation, estrogen, diabetes, and glucocorticoids. Skin and bone collagen are pathologically modified by aging, drugs, and metabolic diseases, such as diabetes. The structural similarities between the skin and bone and the crosstalk controlling their mutual pathological effects have led to the advocacy of the skin-bone axis. Thus, the skin may mirror the health of the bones and conversely, the condition of the skin may be reflected in the bones. From the perspective of the skin-bone axis, the similarities between skin and bone anatomy, function, and pathology, as well as the crosstalk between the two, are discussed in this review. A thorough elucidation of the pathways governing the skin-bone axis crosstalk would enhance our understanding of disease pathophysiology, facilitating the development of new diagnostics and therapies for skin collagen-induced bone disease and of new osteoporosis diagnostics and therapies that enhance skin collagen to increase bone quality and density.

Eccrine Angiomatous Hamartoma Occurring on the Nail Bed.

A 71-year-old woman was referred to our clinic with a 2-month history of pain and exudate from her right first toe. Physical examination revealed a subungual nodule that elevated the nail plate and produced distal onycholysis. We performed onychectomy and removed the nodule. A histopathological specimen from the nodule showed hyperkeratosis and acanthosis in the epidermis, papillomatosis and dilated vessels in the superficial dermis, and aggregation of eccrine glands in the mid-dermis. Based on these findings, a diagnosis of eccrine angiomatous hamartoma (EAH) was made. EAH is a rare cutaneous hamartoma that is histologically characterized by proliferation of eccrine glands and vascular components. To our knowledge, EAH occurring in the subungual region has not been reported. The pathogenesis of acquired EAH has not been completely elucidated, but several cases have been reported to be caused by external stimuli. Although the subungual area generally has no sweat glands, our case suggests that a traumatic stimulus can induce EAH anywhere including regions where sweat glands are normally not found.

Ultrastructural and morphological analysis during progression of Bowen disease reveals a complex interplay between hyperkeratosis, cytokeratin expression, host immunity and amyloid deposition.

BACKGROUND: Bowen disease, one of the common skin cancers, is defined as squamous cell carcinoma in situ, characterized by atypical keratinocytes occupying the full thickness of the epidermis, and predominantly occurs on sun-protected skin. There is no existing data on the impact of tumour and immune cell interactions or cytokeratin expression on the pathology of Bowen disease. OBJECTIVES: We analysed dynamic changes in cytokeratin expression and immune cell composition during the development and progression of Bowen disease. MATERIALS & METHODS: Analysis was performed using immunohistochemistry and electron microscopy for samples from 140 patients with Bowen disease and 20 patients with invasive squamous cell carcinoma. We evaluated cytokeratin expression, the number of infiltrating immune cells and amyloid deposition by immunohistochemistry, and the ultrastructural relationship between tumour cells and immune cells by electron microscopy. RESULTS: The results showed that the expression of CK14 is associated with tumour progression, keratotic status and amyloid deposition and that the expression of CK10 is associated with accumulation of immune cells in Bowen disease. The findings of electron microscopy indicated repeated battles involving immune cells in response to tumour invasion. CONCLUSION: The expression of cytokeratins, hyperkeratosis, inflammatory infiltration and amyloid deposition are useful findings indicating the "stage" in Bowen disease.

Survival rates of systemic interventions for psoriasis in the Western Japan Psoriasis Registry: A multicenter retrospective study.

Psoriasis affects approximately 0.3% of the Japanese population. Recently, various effective systemic drugs have become available, and the continuation of a given treatment has become critical because of the chronic nature of psoriasis. Factors affecting drug survival (the time until treatment discontinuation) in psoriasis treatment include efficacy, safety, ease of use, and patient preference. In the present study, the authors retrospectively surveyed a multifacility patient registry to determine the real-world evidence of the survival rate of systemic interventions for psoriasis treatment. Patients with psoriasis who visited 20 facilities in the Western Japan area between January 2019 and May 2020 and gave written consent were registered as study participants, and their medical history of systemic interventions for psoriasis (starting from 2010) was retrospectively collected and analyzed. The drugs investigated were adalimumab, infliximab, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, cyclosporine, and apremilast. When drugs were discontinued, the reasons were also recorded. A total of 1003 patients with psoriasis including 268 with psoriatic arthritis (PsA) were enrolled. In biologics, more recently released drugs such as interleukin 17 inhibitors showed a numerically higher survival rate in the overall (post-2010) analysis. However, in the subset of patients who began treatment after 2017, the difference in the survival rate among the drugs was smaller. The reasons for discontinuing drugs varied, but a loss of efficacy against dermatological or joint symptoms were relatively frequently seen with some biologics and cyclosporine. The stratification of drug survival rates based on patient characteristics such as bio-naive or experienced, normal weight or obese, and with or without PsA, revealed that bio-experienced, obese, and PsA groups had poorer survival rates for most drugs. No notable safety issues were identified in this study. Overall, the present study revealed that the biologics show differences in their tendency to develop a loss of efficacy, and the factors that negatively impact the survival rate of biologics include the previous use of biologics, obesity, and PsA.

Clinical characteristics of patients with psoriasis with family history: A multicenter observational study.

Previous studies on family history of psoriasis showed that patients with a family history have an earlier onset of the disease, but such studies in Japan are still limited. To elucidate the characteristics of patients with familial psoriasis, we studied the family history of patients with psoriasis using the West Japan Psoriasis Registry, a multi-institutional registry operated by 26 facilities in the western part of Japan, including university hospitals, community hospitals, and clinics. This study enrolled 1847 patients registered between September 2019 and December 2021, with 199 (10.8%) having a family history of psoriasis. Patients with a family history of psoriasis had significantly earlier onset of the disease than those without a family history. Furthermore, patients with a family history of psoriasis had significantly longer disease duration. Psoriatic arthritis (PsA) was significantly more common in patients with a family history (69/199, 34.7%) than in those without a family history (439/1648, 26.6%) (adjusted P = 0.023). A subanalysis of patients with PsA revealed a significant difference in the patient global assessment (PaGA) score in Fisher's exact test and adjusted test. The numbers of patients with PaGA 0/1 were 29 (43.3%) and 172 (39.9%) in patients with PsA with and without family history of psoriasis, respectively, whereas the numbers of patients with PaGA 3/4 were 13 (19.4%) and 145 (33.6%) in patients with PsA with and without family history of psoriasis, respectively. Other disease severity variables did not show a difference between the two groups. Our findings suggest that genetics play a larger role in the development of PsA than in the development of psoriasis vulgaris. Most cases of PsA occur in patients who already have psoriasis, therefore dermatologists should pay attention to joint symptoms, especially in patients with psoriasis who have a family history of psoriasis.

Dual role of basophils in the pathogenesis of bullous pemphigoid elucidated by pathological and ultrastructural studies

Background: Bullous pemphigoid (BP), one of the most common autoimmune blistering disorders, is characterized by early erythematous and bullous lesions. Histopathologically, eosinophilia in the dermal tissue is a common finding in BP. In addition, basophils infiltrate the BP skin lesion. Although basophils are involved in the induction of type 2 immunity along with eosinophils, their role in both the erythema and blister, as well as the chronology of their involvement, have not been investigated. Objectives: To elucidate the role of basophils in BP development and resolution by performing early- and late-phase histopathological analysis of BP. Materials & Methods: A total of 25 patients with BP who underwent biopsy for both erythema and bullous lesions and were not taking oral steroids at the time of biopsy, were selected. Biopsy specimens of the erythematous (inflammatory) and bullous (resolution) phases were compared by histopathology, immunohistochemistry and electron microscopy. Results: During the early phase of BP, the number of basophils positively correlated with the number of eosinophils compared with other immune cells. In the late phase (bullous phase) of BP, the number of basophils significantly increased and more cell-cell contact between the basophils and M2 macrophages was noted, compared to the early phase Conclusions: Basophils are involved in the development of BP and its resolution, in part, via cell-cell contact with eosinophils or M2 macrophages, as demonstrated by pathological analysis.

Infiltrative Erythemas and Nodules on a Unilateral Cheek Following Inappropriate Use of a Topical Steroid.

A 50-year-old Japanese woman referred to us with erythematous nodules on her left cheek. She had been treated with topical corticosteroids on her left cheek at a previous local clinic for 4 years. A skin biopsy specimen from a nodule showed perifolliculitis and folliculitis with a destruction of hair follicle without epidermal involvement. Based on the patient's history of the long-term topical corticosteroids and physical examination, we finally diagnosed this case as unilateral steroid-induced rosacea-like dermatitis (SIRD). She stopped topical steroid and was treated with topical application of benzoyl peroxide. One and a half year after starting the treatment, the nodules were flattened. Use of long-term and only unilateral application of topical corticosteroids probably resulted in unique clinical findings in our case. Given the broad clinical differential diagnosis, our case highlights the importance of appropriate application of topical steroids as well as histopathological analysis on any facial erythematous nodules.

Limitation of Using Ultrasonography After Positive Sentinel Lymph Node Biopsy in a Patient with Melanoma in the Detection of Lymph Node Metastasis.

Recent studies have shown that complete lymph node dissection (CLND) performed immediately did not improve the overall survival in patients with sentinel lymph node (LN)-positive melanoma. According to these results, nodal observation with ultrasonography becomes standard. However, it still has some limitations for detection of metastatic LNs. A 74-year-old woman was diagnosed with acral lentiginous melanoma of her left sole. The sentinel LN was positive for metastasis, but she refused CLND. Sixteen months after operation, ultrasonography showed an abnormal LN in the inguinal region. There was no other abnormal LNs around the LN. We resected the abnormal LN. The resected LN was black in color, and the adjacent LN that showed normal appearance in ultrasonography was also black. A recent study showed only 6.6% sensitivity in preoperative ultrasonographic detection of metastatic melanoma in a LN. We should keep in mind the limitation of ultrasonography for detection of a metastatic LN.

Expression of Programmed Death-Ligand 1 and Programmed Death-1 in Patients with Extramammary Paget's Disease.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare skin cancer and sometimes has fatal prognosis. For progressive cases, therapeutic options are limited. In recent years, treatment with an anti-programmed death-1 (PD-1) antibody has improved the prognosis of various malignancies. In addition, correlations between PD-ligand 1 (PD-L1) expression in tumor cells and favorable responses to anti-PD-1 therapy have been reported for several cancers. There have been a few case series of analysis of PD-L1 expression in patients with EMPD. AIMS: The purpose of this study was to investigate the relationship between the EMPD and PD-L1/PD-1 expression in Japanese EMPD patients. MATERIALS AND METHODS: We investigated 39 patients with EMPD by immunohistochemical staining of PD-L1 and PD-1. We counted the number of tumor cells that were positive for PD-L1 and the number of tumor-infiltrating mononuclear cells (TIMCs) that were positive for PD-L1 and PD-1. We also analyzed correlations between the expression of PD-L1 and PD-1 in EMPD and patients' characteristics. RESULTS: We found that none of the Paget's cells expressed PD-L1. All of the specimens contained TIMCs, and some of the TIMCs expressed PD-L1 and PD-1. However, there was no correlation between the expression of PD-L1/PD-1 in TIMCs and patients' characteristics. CONCLUSION: Although tumor cells did not express PD-L1 and the expression of PD-L1/PD-1 in TIMCs did not correlate with patients' characteristics, future clinical studies should be carried out to explore another immune escape pathway in EMPD.