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This article discusses the progression of parapsoriasis, a group of diseases that includes pityriasis lichenoides (PL), small-plaque parapsoriasis (SPP), and large-plaque parapsoriasis (LPP), to mycosis fungoides (MF), a type of cutaneous T cell lymphoma (CTCL). While PL rarely progresses to MF, SPP and LPP have occasionally been observed to progress to MF. The article presents a case study of a Japanese man with LPP who eventually developed MF, and analyzes the clonality of T cell receptors (TCRs) in skin samples over time. The study suggests that TCR clonality may be a key factor in differentiating parapsoriasis from MF, but further research is needed to validate these findings. [Extracted from the article]

The clinical characteristics and pathogenesis of acral melanoma of the foot (AMF) have not been sufficiently elucidated. Clinical or subclinical persistent inflammation of the feet is caused by dermatophytosis of the feet (DPF). Persistent inflammation is potentially associated with oncogenesis. Moreover, diabetes has been reported to be associated with the development of dermatophytosis and cancer. The present study aimed to elucidate the clinical association between DPF and AMF, with consideration of diabetes. The medical records of 114 Japanese patients were retrospectively examined and divided into an AMF group (n = 30) and a control group consisting of patients with foot diseases other than melanoma (n = 84). Microscopic DPF screening was performed on all patients who reported symptoms in the foot, with or without AMF. Patients underwent a microscopic test to detect the presence of dermatophytes, and the diagnosis of DPF was made based on a positive result. In the AMF group, 18 (60.0%) and eight (26.7%) patients had DPF and diabetes, respectively. Four patients (13.3%) had both DPF and diabetes. In the control group, 25 (29.8%) and 11 (13.1%) patients had DPF and diabetes, respectively. Five patients (6.0%) had both DPF and diabetes. Univariate analyses showed a significantly higher prevalence of DPF in the AMF group than in the control group (odds ratio, 3.540; p = 0.003, Pearson χ2 test). Furthermore, multivariate analyses of sex, body mass index, DPF, and diabetes revealed DPF as a significant factor associated with AMF (odds ratio, 4.285; p = 0.002, logistic regression analysis). The hyperkeratotic type of DPF was more frequently observed in patients with AMF than in control patients (odds ratio, 11.083; p < 0.001, Pearson χ2 test). In conclusion, the present study found a significantly higher prevalence of DPF, especially its hyperkeratotic type, in patients with AMF. DPF may be associated with AMF pathogenesis. [ABSTRACT FROM AUTHOR]

Patients with psoriatic arthritis (PsA) often experience comorbid, irreversible joint destruction, therefore early diagnosis and treatment of PsA are important. The diagnosis requires a comprehensive assessment, which includes an interview, a physical examination, a visual examination of the skin and nails, a blood test, and an imaging test. To clarify how patients with PsA are actually diagnosed and how physicians collaborate among clinical departments, we conducted a web‐based questionnaire survey of 500 physicians (dermatologists, rheumatologists, and orthopedists) frequently involved in PsA treatment in Japan. The survey showed that those patients are rarely confirmed to have axial arthritis, peripheral arthritis, enthesitis, or dactylitis by general dermatology practitioners (GP dermatologists). Overall, <60% of patients suspected of having PsA underwent PsA examination by GP dermatologists more than once every 6 months; this percentage is lower than that of patients who underwent PsA examination by rheumatologists and orthopedists. The Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire is the most commonly used for PsA screening. However, users of PASE were only 11.0%, 25.3%, 14.8%, and 24.1% of GP dermatologists, attending dermatologists in hospitals (HP dermatologists), rheumatologists, and orthopedists, respectively. While >80% of HP dermatologists, rheumatologists, and orthopedists used imaging tests (ultrasound, X‐ray, and magnetic resonance imaging) for PsA screening, only 40% of GP dermatologists performed imaging tests. Regarding the demands on the healthcare environment of PsA treatment, early diagnosis and treatment for PsA are crucial in every clinical department. The present study showed that GP dermatologists rarely perform imaging tests or confirm a PsA diagnosis, thus patients may miss out on appropriate treatment through collaboration among clinical departments and step‐up therapy. Because patients with PsA present diverse comorbid clinical symptoms, early diagnosis, including routine imaging tests, and appropriate treatment in collaboration with other experts are necessary. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We encountered an immunocompromised patient with severe respiratory disease immediately after the onset of varicella. Varicella zoster virus infection may be associated with more severe immunosuppressive condition. [ABSTRACT FROM AUTHOR]

Apalutamide is an antiandrogen used to treat prostate cancer. Although it sometimes induces mild cutaneous adverse events and occasionally severe ones, clinical differences between severe and mild cases remain unclear. To assess the risks in patients experiencing apalutamide‐related cutaneous adverse events (ARCAEs), we aimed to characterize severe and mild ARCAEs in terms of onset time and lymphocyte transformation test (LTT) for apalutamide. We reviewed 41 ARCAE cases: 24 from our institute and 17 from the literature, comprising (i) eight severe cases including six with toxic epidermal necrolysis, one with acute generalized exanthematous pustulosis, and one with drug reaction with eosinophilia and systemic symptoms, and (ii) 33 mild cases. Patients with evere cases developed ARCAEs significantly earlier than patients with mild cases (5.2 vs 9.6 weeks). No severe cases appeared ≥8 weeks after initiation of apalutamide. LTTs showed positive results in two of seven mild cases (28.6%) and four of four severe cases (100.0%). In conclusion, we found that severe ARCAEs are characterized by earlier onset and LTT positivity. Dermatologists and urologists should pay special attention to patients who develop ARCAEs <8 weeks after initiating apalutamide and/or show positive LTT results. [ABSTRACT FROM AUTHOR]

This article discusses the relationship between the number and location of itchy sites and the severity of atopic dermatitis (AD). The study used the 5-D Itch Scale (5-DIS) to measure the distribution of itchy sites on AD patients. The results showed that the total score of 5-DIS was highly correlated with itch visual analogue scale (VAS), indicating that the number of itchy sites is an important factor in evaluating the condition of AD. Additionally, specific sites such as the abdomen, chest, groin, and buttocks were found to have a strong association with increased itch VAS. The study suggests that dermatologists should consider reducing the number of itchy sites as a treatment goal. [Extracted from the article]

Key Clinical Message: We report a case of leukemia cutis showing annular erythema during the course of Philadelphia chromosome‐positive acute B‐lymphoblastic leukemia. The annular appearance may be developed by immunomodulatory effects of blinatumomab. [ABSTRACT FROM AUTHOR]

This is the English version of Japanese guidance for the use of oral Janus kinase (JAK) inhibitors (JAK1 and tyrosine kinase 2 [TYK2] inhibitors) in the treatments of psoriasis. Several cytokines, such as interleukin (IL)‐6, IL‐7, IL‐12, IL‐21, IL‐22, IL‐23, interferon (IFN)‐α, and IFN‐γ, are involved in the pathogenesis of psoriasis (including psoriatic arthritis). As oral JAK inhibitors hinder the JAK‐signal transducers and activators of transcription signal transduction routes involved in the signal transduction of these cytokines, they may be effective for the treatment of psoriasis. JAK has four types: JAK1, JAK2, JAK3, and TYK2. Regarding the use of oral JAK inhibitors for the treatment of psoriasis in Japan, indications of the JAK1 inhibitor upadacitinib were extended also to psoriatic arthritis in 2021, and the use of the TYK2 inhibitor deucravacitinib for plaque‐type psoriasis, pustular psoriasis, and erythrodermic psoriasis became covered by health insurance in 2022. This guidance was developed for board‐certified dermatologists who specialize in the treatment of psoriasis and to promote the proper use of oral JAK inhibitors. In the package inserts and guides for appropriate use, upadacitinib and deucravacitinib are classified as a "JAK inhibitor" and a "TYK2 inhibitor", respectively, and it is possible that there may be differences in safety between the two drugs. The safety of these drugs will be evaluated for the future by the postmarketing surveillance for molecularly targeted drugs for psoriasis of the Japanese Dermatological Association. [ABSTRACT FROM AUTHOR]

Melanoma is one of the most severe skin cancers, derived from melanocytes. Among various therapies for melanoma, adoptive immunotherapy using tumor‐infiltrating lymphocytes/chimeric antigen receptor‐T cells (TCs) is advanced in recent years; however, the efficacy is still limited, and major challenges remain in terms of safety and cell supply. To solve the issues of adoptive immunotherapy, we utilized induced pluripotent stem cells (iPSCs), which have an unlimited proliferative ability and various differentiation capability. First, we monoclonally isolated CD8+ TCs specifically reactive with NY‐ESO‐1, one of tumor antigens, from the melanoma patient's monocytes after stimulated with NY‐ESO‐1 peptide by manual procedure, and cultured NY‐ESO‐1‐specific TCs until proliferated and formed colonies. iPSCs were consequently generated from colony‐forming TCs by exogenous expression of reprogramming factors using Sendai virus vector. After the RAG2 gene in TC‐derived iPSCs (T‐iPSCs) was knocked out for preventing T‐cell receptor (TCR) rearrangement, T‐iPSCs were re‐differentiated into rejuvenated cytotoxic TCs. We confirmed that TCR of T‐iPSC‐derived TC was maintained as the same of original TCs. In conclusion, T‐iPSCs have a potential to be an unlimited cell source for providing cytotoxic TCs. Our study could be a "touchstone" to develop iPSC‐based adoptive immunotherapy for the treatment of melanoma for the future clinical use. [ABSTRACT FROM AUTHOR]

This is the English version of Japanese guidance for use of biologics for psoriasis (the 2022 version). As the first biologics for psoriasis in Japan, infliximab and adalimumab, anti‐tumor necrosis factor‐α antibodies, became available in the field of dermatology in 2010, followed by ustekinumab, an anti‐interleukin (IL)‐12/IL‐23p40 antibody, which was launched in Japan in 2011. Moreover, after 2015, three IL‐17 inhibitors, the IL‐17A antibody preparations secukinumab and ixekizumab, and an anti‐IL‐17 receptor antibody preparation brodalumab were marketed. Furthermore, after 2018, the anti‐IL23p19 antibody preparations guselkumab and risankizumab, the TNF inhibitor certolizumab pegol, the IL‐23 inhibitor tildrakizumab, and the anti‐IL‐17A/F antibody bimekizumab were marketed. It is important for physicians to select appropriate biologic therapy for each psoriatic patient after due consideration of disease factors, treatment factors, and patient background factors, sharing such information with patients. The followings can be listed as points to be considered for the selection of biologics: drug effects (e.g., strength of effectiveness, time to onset of effectiveness, effectiveness against arthritis, primary failure, secondary failure), safety (e.g., infections, administration‐related reactions, and relationships with other comorbidities), convenience for patients (e.g., hospital visit intervals, self‐injection, maintenance therapy at clinics, feasibility of drug discontinuation/re‐administration), and payment (medical costs) borne by patients. This guidance has been prepared with the aim of allowing dermatologists experienced in the treatment of psoriasis to use biologics appropriately according to the circumstances of individual patients after consideration of the above‐mentioned factors. [ABSTRACT FROM AUTHOR]

Psoriasis patients have been reported to have a higher prevalence of nonalcoholic fatty liver disease (NAFLD), therefore detection at an early stage is important since it may progress to hepatic cirrhosis or hepatocellular carcinoma. We evaluated liver fat accumulation in patients with moderate to severe psoriasis by chest computed tomography (CT). The images were taken for screening purposes prior to the start of any biologics. The prevalence of NAFLD in patients with psoriasis vulgaris, psoriatic arthritis, and control subjects was 19.4%, 33.3% and 9.8%, respectively (P = 0.004). The mean CT score in psoriasis patients was significantly lower (51.684 ± 12.778) than that in control subjects (61.204 ± 9.498, P < 0.001). Multivariate logistic regression analysis showed that only CT scores were associated with the presence of psoriasis (P = 0.001). No significant relationship was observed between the Psoriasis Activity and Severity Index scores and CT scores of psoriasis patients (P = 0.055), suggesting that the presence of psoriasis may contribute to the pathogenesis of NAFLD. By analysis of chest CT imaging, our study successfully assessed liver fat accumulation. Chest CT is a useful diagnostic tool for the quantitative measurement of fat accumulated in the liver, enabling the early noninvasive detection of NAFLD and early therapeutic intervention. [ABSTRACT FROM AUTHOR]

Voriconazole is commonly administered for a long period to patients receiving immunosuppressive therapy. Although voriconazole potentially induces skin cancers in association with sun exposure, this has not yet been examined in detail in a single ethnic patient group. Therefore, the present study investigated the risk of developing squamous cell carcinoma (SCC) in Japanese patients with voriconazole‐related actinic keratosis (AK) and the prognosis of Japanese patients with voriconazole‐related SCC. We retrospectively examined 37 Japanese patients with AK, including five voriconazole‐treated patients (mean age, 57.9 ± 16.3 years) and 32 non‐treated patients (74.9 ± 9.2 years), and 18 Japanese patients with SCC, including four voriconazole‐treated patients (55.4 ± 16.7 years) and 14 non‐treated patients (74.1 ± 10.7 years). Among the 37 patients with AK, SCC developed in five, including four with a history of treatment with both voriconazole and immunosuppressive agents, independent of AK progression. In these four patients, the mean period from the diagnosis of AK to that of SCC was 13.8 ± 11.6 months. Kaplan––Meier analyses showed that the risk of developing SCC was significantly higher in patients with both voriconazole and immunosuppressants/corticosteroid‐treated patients with AK than in non‐voriconazole‐treated patients with AK (the Log‐rank test, p < 0.001). The analyses also showed that the mortality rate was significantly higher in patients with both voriconazole and immunosuppressants/corticosteroid‐treated patients with SCC than in non‐voriconazole‐treated patients with SCC (p = 0.018). The present results suggest that voriconazole‐related AK precedes the development of cutaneous SCC and voriconazole‐related SCC leads to a poor prognosis under the immunosuppressive condition. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case report provides evidence that Waldenström's macroglobulinemia may cause cutaneous manifestations represented as papules/nodules through the development of light chain amyloidosis. Here, we report a case of a 67‐year‐old man. [ABSTRACT FROM AUTHOR]

Cancer‐associated hypercalcemia commonly occurs through abnormal secretions of parathyroid hormone‐related protein (PTHrP) from cancer cells. Several cases of PTHrP‐producing melanoma causing hypercalcemia have been reported; however, effective management of PTHrP‐producing BRAF wild‐type melanoma causing hypercalcemia after immune checkpoint inhibitor (ICI) failure is unclear. We report a case of PTHrP‐producing BRAF wild‐type melanoma leading to oncological emergency by hypercalcemia that was successfully treated with dacarbazine after ICI failure. A 65‐year‐old Japanese woman had advanced BRAF wild‐type melanoma that was refractory to ICI, and then led to hypoxia through exacerbated lung metastases and pleural effusion. Moreover, hypercalcemia appeared in parallel with increase of the serum PTHrP level. Dacarbazine was administered, and after the first administration, the pleural effusion was gradually decreased and hypoxia rapidly disappeared, and the serum calcium and PTHrP levels were improved within normal limits. Dacarbazine after ICI failure is potentially a useful option for oncological emergency due to progression of BRAF wild‐type melanoma including PTHrP‐producing types. Dacarbazine should be reevaluated as a therapeutic option for oncological emergency in patients with BRAF wild‐type melanoma after ICI failure. [ABSTRACT FROM AUTHOR]

Necrotizing fasciitis is a rare and severe infectious disease that is often fatal and is characterized by the extensive necrosis of subcutaneous tissue and fascial planes. A number of clinical parameters have been intensively investigated to diagnose and assess the severity and prognosis of necrotizing fasciitis. Since it currently remains unclear whether these parameters are also abnormal before disease onset, the present study investigated this issue. We retrospectively recruited 38 patients, including 12 and 26 patients with necrotizing fasciitis and cellulitis, respectively. The results of routine blood examinations were collected at disease onset and also at baseline, which was defined as the time point before disease onset. No significant differences were observed in age or sex between the necrotizing fasciitis and cellulitis groups. However, significant differences were noted in the levels of hemoglobin, lymphocyte count, platelet count, neutrophil‐to‐lymphocyte ratio, sodium, creatinine, albumin, D‐dimer, and Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score at disease onset. Significant differences were also observed in the levels of hemoglobin, lymphocyte count, monocyte count, platelet count, creatinine, D‐dimer, and LRINEC score at baseline. Hemoglobin, platelet count, C‐reactive protein, creatinine, albumin, and D‐dimer levels were already abnormal at baseline in the necrotizing fasciitis group. In conclusion, the present results revealed precritical abnormalities in routine blood parameters in patients with necrotizing fasciitis. Therefore, individuals predisposed to necrotizing soft tissue infection may be identified prior to disease onset. [ABSTRACT FROM AUTHOR]

Ultrasonography and magnetic resonance imaging (MRI) are useful for diagnosing psoriatic arthritis (PsA). However, ultrasonography depends on the skill of the operator and MRI is often disturbed by artifacts when distal interphalangeal joints are examined. Although iodine‐enhanced dual‐energy computed tomography (DECT) has the potential to diagnose PsA without these disadvantages, its usefulness over ultrasonography has not yet been examined in detail; therefore, the present study was conducted to address this issue. The acral joint of 13 PsA patients, which was the most severely affected, was scanned with imaging devices. Ultrasonography was performed with a high‐frequency linear 18‐MHz probe. Iodine‐enhanced DECT was conducted in the DE mode with iohexol as a contrast material. Psoriatic Arthritis Screening and Evaluation (PASE) scores were recorded. Synovitis and periarticular inflammation delineated with iodine‐enhanced DECT correlated with the loss of the fibrillar pattern delineated with ultrasonography (p = 0.033 and 0.002, respectively). Peritendinitis delineated with iodine‐enhanced DECT also correlated with tendon thickening delineated with ultrasonography (p = 0.011). Iodine uptake did not correlate with Doppler signal or PASE scores. In conclusion, the present results demonstrated that the qualitative findings of iodine‐enhanced DECT correlated with those of ultrasonography in PsA patients, whereas quantitative findings did not. Iodine‐enhanced DECT may be an alternative imaging modality for the diagnosis of PsA. [ABSTRACT FROM AUTHOR]

While many patients with psoriasis are candidates for topical agents, long‐term treatment effects are unclear. This systematic review evaluated global findings from clinical trials and real‐world studies of topical calcipotriol and the two‐compound formulation of calcipotriol and betamethasone dipropionate for mild‐to‐moderate plaque psoriasis (including scalp psoriasis). PubMed, Embase and MEDLINE were searched for relevant English‐language publications along with Chinese, Japanese, Korean and Latin American publication databases. Identified articles were screened by title and abstract against predefined inclusion/exclusion criteria. A narrative synthesis of key efficacy and safety findings from the full papers of selected publications was developed. Thirty‐seven relevant papers were identified (25 English, 11 Chinese and one Japanese‐language study) including 28 randomized controlled trials. While there was significant heterogeneity in study length, treatment intensity and clinical measures, following a critical review of the published data combined with expert opinion, the following clinical practice recommendations were agreed in order to assist healthcare providers: in adults, long‐term treatment with calcipotriol/betamethasone dipropionate is well tolerated and efficacious for up to 1 year on an 'as needed' basis, and for up to 16 weeks on a fixed‐treatment regimen. Calcipotriol is also well tolerated and efficacious when used long term (up to 52 weeks) 'as needed' and for up to 20 weeks on a fixed‐treatment regimen. Used on an 'as needed' basis for up to 1 year, the safety and efficacy profile of fixed‐dose combination calcipotriol/betamethasone dipropionate is more favorable than calcipotriol alone; regular consultation between patients and their dermatologist/primary care physician is required to review psoriasis symptoms and adjust treatment accordingly; a specific treatment goal should be agreed on initiation of topical agent(s) to determine when long‐term treatment can begin or if a regimen change is warranted; and application frequency during the continued treatment phase should consider the patients' treatment expectations and goals. [ABSTRACT FROM AUTHOR]

Background: Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive inherited disorder caused by biallelic variants in the CDH3 gene encoding P‐cadherin. Here, we report two Japanese sibling patients with HJMD. Methods: Whole‐exome sequencing (WES) was performed to identify disease‐causing variants. In addition, ophthalmic and dermatological examinations were performed to classify the phenotype of each patient. Results: The WES analysis revealed novel compound heterozygous CDH3 variants [c.123_129dupAGGCGCG (p.Glu44fsX26) and c.2280+1G>T] in both patients; the unaffected, nonconsanguineous parents each exhibited one of the variants. Both patients showed the same clinical findings. Ophthalmologically, they exhibited progressive loss of visual acuity and chorioretinal macular atrophy, as examined with fundoscopy, fundus autofluorescence imaging, and optical coherence tomography. Full‐field electroretinography, assessing generalized retinal function, revealed nearly normal amplitudes of both rod‐ and cone‐mediated responses. Multifocal electroretinography, reflecting macular function, showed extremely decreased responses in the central area, corresponding to the chorioretinal atrophy. Dermatological examination revealed diffuse thinning of the scalp hair, which was sparse and fragile. Conclusion: This is the first report of Japanese patients with HJMD and novel compound heterozygous truncating variants in CDH3. Our findings can expand the knowledge and understanding of CDH3‐related HJMD, which could be helpful to ophthalmologists and dermatologists. [ABSTRACT FROM AUTHOR]

Interleukin (IL)‐17 plays critical roles in the pathogenesis of both psoriasis and interstitial pneumonia (IP). We hypothesized that anti‐IL‐17 biologics might suppress both clinically relevant and latent IP activity and decrease Krebs von den Lungen‐6 (KL‐6) level in psoriasis patients. We aimed to elucidate the effects of anti‐IL‐17 biologics on KL‐6 levels. We retrospectively analyzed the clinical data of psoriasis patients treated with anti‐IL‐17 biologics. KL‐6 levels were measured before treatment (baseline) and at 3 and 6 months after the initiation of the treatment, and ratios of KL‐6 levels at each time point to the baseline levels were calculated. Chest computed tomography (CT) was performed on patients with coexisting IP. The clinical characteristics and radiographic findings were evaluated. A total of 294 psoriasis patients were treated with anti‐IL‐17 biologics. Baseline KL‐6 levels were higher than 401 U/mL in 34 patients (high baseline KL‐6 group). While anti‐IL‐17 biologics did not affect KL‐6 levels and ratios of KL‐6 to the baseline levels at any time point in the overall study population, they decreased both KL‐6 levels and ratios at 6 months after the initiation of the treatment in the high baseline KL‐6 group. A total of 10 patients with coexisting IP showed decreasing ratios of KL‐6 to the baseline levels at 6 months without affecting coexisting IP in CT performed at 3–12 months. Anti‐IL‐17 biologics decreased KL‐6 levels in the high baseline KL‐6 group regardless of recognizable IP. A decrease in KL‐6 levels was not associated with a radiographic improvement of IP, which should be examined in large numbers with long‐term observations in future studies. [ABSTRACT FROM AUTHOR]

Diffuse cutaneous mastocytosis (DCM) is the least common subtype of cutaneous mastocytotis and is generally more severe than other subtypes. We herein report a case of DCM with the consequence of a long‐term follow‐up. A 4‐month‐old boy visited with a 3‐month history of diffuse erythema that gradually worsened. Darier's sign was positive. The plasma histamine level was 4.95 ng/mL, and the serum tryptase and c‐Kit (CD117) levels were 33.3 and 27.4 ng/mL, respectively. Histopathology of the biopsied specimen showed dermal papillary edema and infiltration of mast cells identified by c‐Kit and toluidine blue staining. Amplification and direct sequencing of genomic DNA extracted from the skin biopsy specimen revealed the presence of a deletion of codon 419 in exon 8 (c.1255_1257delGAC [p. Asp419del]). There was no evidence of systemic infiltration of mast cells in this case, and we started topical corticosteroid and oral antihistamine with the diagnosis of DCM. Diffuse erythema subsided constantly with age in parallel with chronological decline of serum tryptase level, and it is no longer apparent presently at the age of 7 years, leaving only faint brown spots. Blister formation did not occur throughout the course. Our case indicates that spontaneous resolution can be expected even in DCM after a long period of time, and that serum tryptase level serves as a good surrogate marker to monitor the clinical course. [ABSTRACT FROM AUTHOR]

We herein describe a 68‐year‐old man with follicular mucinosis. A dermoscopic examination showed multiple, round, brownish yellow dots with a whitish rim in the follicular ostium and red dots in the interfollicular area. This case report is the first to suggest that follicular mucinosis shows these dermoscopic findings. [ABSTRACT FROM AUTHOR]

CD30‐positive large cell transformation that occurs in early mycosis fungoides potentially possesses characteristics of spontaneous regression as with CD30‐positive lymphoproliferative disorders. Such transformation may not relate to poor prognosis. [ABSTRACT FROM AUTHOR]

Imatinib mesylate seemed to inhibit development of cutaneous neurofibromas (c‐NFs) and promote growth of pre‐existing c‐NFs in our neurofibromatosis type 1 case. This report potentially provides new findings in the effects of imatinib mesylate. [ABSTRACT FROM AUTHOR]

Cutaneous adverse drug reactions (cADR) should be appropriately managed in drug administration. LANSAP®, Rabecure® and VONOSAP® are currently used for Helicobacter pylori eradication therapy. Here, we examined the characteristics of cADR caused by these drugs using data from the Pharmaceuticals and Medical Devices Agency (PMDA). Periods subject to analyses were set according to the year of release of these drugs: (i) from 2008 to 2017 for LANSAP; (ii) from 2014 to 2017 for Rabecure; and (iii) 2017 for VONOSAP. Among all cADR reported to the PMDA, those attributed to LANSAP, Rabecure and VONOSAP accounted for 2.3%, 1.0% and 3.6% of cases, respectively. cADR occurred in patients aged in their 20s or older, with the oldest patients aged in their 60s. Numbers of male and female patients were 28 and 70 for LANSAP, eight and 14 for Rabecure and three and 16 for VONOSAP, respectively. Statistical analyses revealed significant sex differences for LANSAP (P = 0.022) and VONOSAP (P = 0.012), but not for Rabecure (P = 0.729). LANSAP, Rabecure or VONOSAP caused erythema multiforme in the largest population of patients and Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in three patients. Ratios of SJS/TEN were 0.0–5.3% for LANSAP, Rabecure or VONOSAP, but 11.5–44.8% for the corresponding single constituent drugs other than vonoprazan. In conclusion, female sex appears to represent a risk factor for cADR attributed to H. pylori eradication therapy using LANSAP or VONOSAP, although H. pylori eradication therapy without these drugs rarely causes severe cADR. [ABSTRACT FROM AUTHOR]

As the first biologics for psoriasis in Japan, infliximab and adalimumab, anti‐tumor necrosis factor‐α antibodies, became available in the field of dermatology in 2010, followed by ustekinumab, an anti‐interleukin (IL)‐12/IL‐23p40 antibody, which was launched in Japan in 2011. Since 2015, three IL‐17 inhibitors of secukinumab and ixekizumab, anti‐IL‐17A antibodies, and brodalumab, an anti‐IL‐17 receptor antibody, and two anti‐IL‐23p19 antibodies of guselkumab and risankizumab, have also been launched. It is important for physicians to select appropriate biologic therapy for each psoriatic patient after due consideration of disease factors, treatment factors and patient background factors, sharing such information with patients. The following can be listed as points to be considered for the selection of biologics: drug effects (e.g. strength of effectiveness, time to onset of effectiveness, effectiveness against arthritis, primary failure, secondary failure), safety (e.g. infections, administration‐related reactions and relationships with other comorbidities), convenience for patients (e.g. hospital visit intervals, self‐injection, maintenance therapy at clinics, feasibility of drug discontinuation/re‐administration) and payment (medical costs) borne by patients. This guidance has been prepared with the aim of allowing dermatologists experienced in the treatment of psoriasis to use biologics appropriately according to the circumstances of individual patients after consideration of the above‐mentioned factors. [ABSTRACT FROM AUTHOR]

Background: Type 1 interferons (IFNs), including IFN‐β, are widely used in adjuvant therapy for patients who undergo surgery for malignant melanoma to inhibit recurrence and in‐transit metastasis. The precise mechanisms underlying the tumor‐suppressive effects of IFN‐β on melanoma are not yet completely understood. Objective: The purpose was to reveal the mechanisms underlying the tumor‐suppressive effects of IFN‐β via interleukin (IL)‐24. Methods: Genome‐wide oligonucleotide microarray, quantitative real‐time reverse transcription‐polymerase chain reaction (PCR), enzyme‐linked immunosorbent assay and western blotting assay were performed using four melanoma cell lines (A375, RPMI‐7951, SK‐MEL‐5 and SK‐MEL‐1) treated with natural‐type IFN‐β to assess the expression of IL‐24. Proliferation assay was performed using these melanoma cells and IL‐24 knock‐down melanoma cells. Results: Genome‐wide microarray analysis detected candidate genes upregulated in IFN‐β‐sensitive cells after treatment with IFN‐β. We focused on IL‐24 among the candidate genes encoding secretory proteins. Peak IL‐24 mRNA expression completely correlated with the order of sensitivity of melanoma cells to IFN‐β. IFN‐β treatment induced extracellular IL‐24 protein in IFN‐β‐sensitive cells, but did not induce intracellular IL‐24 protein. Knock‐down of IL‐24 changed melanoma cells into IFN‐β‐resistant cells. The expression ratio of IL‐22R1, one of the IL‐24 receptors, correlated with the order of sensitivity of melanoma cells to IFN‐β. Treatment with recombinant human IL‐24 did not have any effects on all the melanoma cell lines. Conclusion: Our data suggest that IFN‐β suppresses the proliferation of melanoma cells through extracellular IL‐24 protein derived from melanoma cells. [ABSTRACT FROM AUTHOR]

The T‐cell immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif domain (TIGIT) is a co‐inhibitory receptor mainly expressed on T cells. Although TIGIT plays an important role in various autoimmune diseases, its role in atopic dermatitis (AD) remains unclear. In this study, we examined the expression levels of TIGIT and their association with clinical features in patients with AD. TIGIT expression on CD4+ T cells, central memory T cells, effector memory T cells and regulatory T cells was determined by flow cytometry. CD4+ T cells exhibited enhanced TIGIT expression in patients with AD compared with healthy individuals. In particular, effector memory T cells and regulatory T cells, but not central memory T cells, exhibited higher TIGIT expression in patients with AD than in healthy individuals. The frequency of TIGIT+ cells among CD4+ T cells was significantly increased in patients with mild AD compared with healthy individuals, while decreased in patients with severe AD. Consistently, the frequency of TIGIT+ cells among CD4+ T cells was negatively correlated with both serum thymus and activation‐regulated chemokine levels and immunoglobulin E levels in patients with AD. Furthermore, TIGIT expression on CD4+ T cells inhibited cell proliferation in patients with AD. These results suggest that TIGIT expression on CD4+ T cells in patients with AD may be increased to suppress chronic cutaneous inflammation. Moreover, TIGIT expression may be impaired in a subset of patients with AD, leading to a deterioration of skin inflammation. Our study may provide new insight into a TIGIT pathway‐based therapeutic approach for AD. [ABSTRACT FROM AUTHOR]

A phase 3, multicenter, open‐label, 52‐week study investigated the efficacy and safety of adalimumab 80 mg at week 0 followed by adalimumab 40 mg every other week (option to escalate to 80 mg when necessary) in Japanese patients with generalized pustular psoriasis (GPP). Adults (aged 15–75 years) with GPP, total skin score (overall erythema area, erythema area with pustules, and edema area) of 3 or more, and erythema with pustules (skin score, ≥1) based on the 2014 Japanese Dermatological Association severity index of GPP were enrolled. The primary efficacy end‐point was clinical response at week 16 (non‐responder imputation), defined as achieving remission (total skin score, 0) or improvement from baseline (reduction of ≥1 point from a baseline total skin score of 3 or ≥2 points from a baseline total skin score of ≥4). Of 10 enrolled patients (mean disease duration, 10.6 years), seven patients, including three with the dose escalated to 80 mg every other week before week 15, achieved clinical response at week 16, and five achieved clinical response at week 52. Mean change from baseline total GPP score was −4.6 at week 16 (n = 8) and −6.0 at week 52 (n = 5); change in total skin score was −3.1 (n = 8) and −4.2 (n = 5), respectively. Nine patients experienced one or more adverse events and three experienced serious adverse events. The most common adverse events were nasopharyngitis, pruritus and hypoalbuminemia. In conclusion, adalimumab was effective and well tolerated for up to 52 weeks in the treatment of Japanese patients with GPP. [ABSTRACT FROM AUTHOR]

Epicardial adipose tissue (EAT) is implicated in the development of coronary atherosclerosis by secretion of inflammatory adipocytokines. Recent studies have shown significantly higher EAT volume in psoriatic patients compared with that in control subjects, but this has not been validated in Japanese patients. We enrolled 86 Japanese patients with moderate to severe psoriasis vulgaris and 31 control subjects, and evaluated EAT volume and coronary artery calcification (CAC) by retrospectively assessing non‐enhanced computed tomography obtained through routine examinations. Both mean EAT volume and mean CAC score were not significantly different between the two groups. Interestingly, however, a subanalysis with those of 50 years of age or less (28 psoriatic patients and seven non‐psoriatic subjects) showed significantly higher mean EAT volume in psoriatic patients. Similarly, the ratio of the presence of at least one CAC was significantly higher in this group. Our findings suggest that Japanese psoriatic patients should also be aware of the cardiovascular risk, and EAT volume and CAC may be useful tools to predict such risk. [ABSTRACT FROM AUTHOR]

Antigenic competition in the skin is a phenomenon in which the current dermatitis is distributed away from the area of previously existing dermatitis. Bullous pemphigoid may present such phenomenon, even if the responsible antigen was the same. [ABSTRACT FROM AUTHOR]

Dear Editor, A case of bullous pemphigoid associated with interstitial pneumonia Bullous pemphigoid is an autoimmune subepidermal bullous disease caused by autoantibodies against adhesion molecules located in the epidermal basement membrane zone including bullous pemphigoid antigen 180 (BP180). Direct immunofluorescence testing of the bullous skin lesion showed weak linear deposition of IgG and strong linear deposition of C3 in the basement membrane zone (Fig d, e). Direct immunofluorescence testing of transbronchial lung biopsy revealed minimal deposition of IgG and some deposition of C3 in a part of basement membrane zone of the alveolar epithelia (Fig g, h). [Extracted from the article]

Abstract: Secukinumab is a fully human monoclonal antibody that can selectively neutralize interleukin‐17A, and its excellent efficacy has been demonstrated in clinical trials for psoriasis. The aim of our study is to assess long‐term efficacy and safety of secukinumab for 52 weeks in real‐world clinical practise in our facility. A total of 83 patients (71 with psoriasis vulgaris and 12 with psoriatic arthritis) were included, and 49 of them were bio‐switched patients. Psoriasis Area and Severity Index (PASI) 75 and PASI‐90 responses were 80% and 64% at week 12, 77% and 65% at week 24, and 76% and 58% at week 52, respectively. No significant differences were observed in efficacy between bio‐naive and bio‐switched patients. Arthralgia showed improvement by week 12 in all patients with psoriatic arthritis with a reduction of serum C‐reactive protein level. Treatment was discontinued in 22% (18/83), including eight patients with no improvement or exacerbation of cutaneous manifestations, one patient with new onset of arthritis and two patients with transient infection. Overall, secukinumab showed a sustained clinical response with an acceptable safety profile through week 52 in Japanese psoriatic patients. [ABSTRACT FROM AUTHOR]

Ustekinumab ( UST) is a treatment option for psoriatic arthritis (PsA), but recent observations indicate that some psoriatic patients may experience new onset of PsA or worsening of pre-existent PsA. We retrospectively analyzed all cases of psoriasis vulgaris (PsV) and PsA treated with UST in our facility between 2011 and 2015. PsA developed in eight out of 179 PsV patients, mostly later than 8 months after initiation of UST. It was generally not severe, and none had received tumor necrosis factor ( TNF)-α inhibitors previously, indicating that the possibility of unmasking pre-existing subclinical arthritis is minimal. The eruptions were well controlled at the time of the onset of arthritis in most cases. Interestingly, those who developed arthritis showed a significantly lower body mass index. Regarding pre-existing PsA, nine PsA patients received UST, and at least partial improvement of PsA could be achieved in two out of three bio-naive and three out of six bio-switched patients from TNF-α inhibitors. PsA was largely more refractory to UST than the eruptions. Altogether, our present study is in agreement with the notion that UST may be less efficient than TNF-α inhibitors for PsA. While UST cannot fully prevent new development of PsA, it is unlikely that UST increases the risk of new onset of PsA as a paradoxical adverse reaction. [ABSTRACT FROM AUTHOR]

Recent studies indicate the presence of systemic inflammation in psoriatic patients, and this inflammatory status is significantly associated with a range of comorbidities. The aim of this study was to evaluate the clinical significance of novel inflammatory biomarkers, neutrophil-lymphocyte ratio ( NLR), platelet-lymphocyte ratio ( PLR) and mean platelet volume ( MPV) in Japanese patients with plaque-type psoriasis (PsV) and psoriatic arthritis (PsA). One hundred and eighty-six patients with PsV and 50 patients with PsA treated with biologics, including infliximab, adalimumab and ustekinumab, were retrospectively analyzed before and after treatment. At baseline, NLR and PLR, as well as C-reactive protein ( CRP), were significantly higher in PsA patients than those in PsV patients, and a significant correlation was found between NLR and PLR. In PsV patients, the NLR-high and PLR-high subgroups exhibited significantly higher Psoriasis Area and Severity Index scores compared with the NLR-low and PLR-low subgroups, respectively, and the NLR-high subgroup also showed higher CRP levels. MPV value was negatively associated with the presence of arthritis, but its association with inflammation was less clear than that of NLR or PLR. After treatment of the patients with biologics for up to 12 months, NLR and PLR decreased promptly in parallel with a decrease of CRP, irrespective of the type of biologics used. Altogether, these results indicate that both NLR and PLR may be useful markers to evaluate systemic inflammation in psoriatic patients. They may serve as simple, convenient and cost-effective biomarkers to monitor the disease course after systemic therapy. [ABSTRACT FROM AUTHOR]

Efficacy and safety profiles of biologics have been established for moderate to severe psoriasis. However, inefficacy or adverse events sometimes require changing the treatment to other biologics. Here, we examine the effectiveness of this strategy. We retrospectively investigated cases requiring switching biologics. We enrolled 275 psoriatic patients treated with biologics between January 2010 and December 2014 in our hospital. Of these, 51 required a switch to another biologic. First-line therapies were infliximab ( IFX, n = 26), adalimumab ( ADA, n = 18) and ustekinumab ( UST, n = 7), and second-line therapies were IFX ( n = 5), ADA ( n = 21) and UST ( n = 25). Reasons for switching were inefficacy ( n = 38), adverse events ( n = 11) and others ( n = 2). The details were primary failure ( n = 15), secondary failure ( n = 23) and infusion reactions ( n = 8). In 49 patients who switched biologics due to inefficacy and adverse events, the mean Psoriasis Area and Severity Index ( PASI) score at week 16 was 4.3 for first-line therapies and 2.9 for second-line therapies ( P < 0.05). Switching to a second biologic therapy to address the first's inefficacy or adverse events often results in significant improvement in moderate to severe psoriasis. [ABSTRACT FROM AUTHOR]

We longitudinally examined the influence of anti-tumor necrosis factor ( TNF)-α treatment on serum levels of KL-6 and surfactant protein-D ( SP-D). The study group comprised 22 patients with psoriasis treated with infliximab or adalimumab and with no history of interstitial lung disease ( ILD). KL-6 and SP-D levels were measured in serum samples. Twelve of the 22 patients (55%) showed at least a 20% increase in KL-6 levels compared with baseline. Of these 12 patients, none exhibited any signs of ILD on chest computed tomography and nine who showed an increase in KL-6 levels (75%) showed at least a 20% increase in SP-D levels. Some patients showed simultaneous increases in KL-6 and SP-D levels after treatment with anti- TNF-α agents. Although these patients may have undetectable or subtle alveolar damage, careful observation is needed. [ABSTRACT FROM AUTHOR]

The number of elderly patients with psoriasis is increasing in Japan. However, biologic treatment is generally considered to be challenging in elderly patients, due to their increased risk of complications compared with younger patients. Our retrospective study aimed to evaluate the safety profile and efficacy of biologics in senior elderly patients (≥75 years old) with psoriasis. The study involved a cohort of 27 patients aged 75-88 years who were being treated with biologics over a period of more than 1 year. Initial biologics administrated to were adalimumab (five cases) and ustekinumab (22 cases). Eight patients discontinued treatment: two developed cancer; one was transferred to hospital; and five others experienced either bone fracture, interstitial pneumonia, cerebral hemorrhage resulting in death, decrepitude or developed hepatopathy following prophylactic tuberculosis treatment. Efficacy, evaluated by the percentage of patients achieving 75% reduction of Psoriasis Area and Severity Index score, was 76.9% at week 16 ( n = 26), 88.0% at week 24 ( n = 25) and 90.5% at week 52 ( n = 21). Biologic treatments thus show clear efficacy in elderly patients with psoriasis, however, the increased frequency of adverse events requires rigorous patient observation. [ABSTRACT FROM AUTHOR]

In the current work, we present our new guideline for the diagnosis and treatment of scabies which we, the Executive Committee convened by the Japanese Dermatological Association, developed to ensure proper diagnosis and treatment of scabies in Japan. Approval of phenothrin topical use under the National Health Insurance in August 2014 led to this action. Permethrin, a topical anti-scabietic medication belonging to the same pyrethroid group as phenothrin, is already in use worldwide. In this guideline, we introduce criteria for a proper diagnosis of scabies, treatment algorithm for common and crusted (hyperkeratotic) scabies, and prevention. The major change from our second edition is the treatment algorithm. As phenothrin is now available, the first-line therapy for common scabies is either topical phenothrin lotion or oral ivermectin. The second-line option for topical treatment is sulfur-containing ointments, crotamiton cream or benzyl benzoate lotion. γ-Benzene hexachloride ointment is no longer provided for clinical use. In an immunosuppressed patient, the treatment option is still the same, but with close follow up. If the symptoms persist, diagnosis and treatment must be reassessed. For hyperkeratotic scabies and nail scabies, removal of thick crust, cutting of nails and occlusive dressing are additionally required. The safety and effectiveness of combined treatment with topical and oral medications are not yet confirmed. Further assessment is needed. In addition to appropriate treatment, it is essential to educate patients and health-care workers and to conduct epidemiological studies to prevent further spread of the disease through effectively utilizing available resources including manpower, finance, logistics and time. [ABSTRACT FROM AUTHOR]

Relapsing polychondritis (RP) is a rare autoimmune-mediated disease characterized by inflammation involving cartilaginous tissues. We report here a case of RP in a 38-year-old Japanese man with 13-year duration of psoriasis vulgaris treated with topical steroids and vitamin D3. The patient presented with tender swelling and erythema of both auricles, and the antibody to type II collagen was detected. The biopsy specimen revealed a dense mixed cell infiltration over the auricular cartilage. We reviewed eight cases with the association of RP and psoriasis, and in all cases the clinical course of psoriasis did not correlate with that of RP. The severity of RP was mild in the majority of cases, and our case was unique in that the patient had no joint symptoms. Adalimumab treatment was effective for both RP and psoriasis. Fat-suppressed contrast-enhanced magnetic resonance imaging was beneficial, not only to demonstrate subclinical inflammation in the nasal septum, but also to subjectively assess the improvement of RP. [ABSTRACT FROM AUTHOR]

The safety and efficacy of adalimumab were evaluated over 24 weeks in Japanese patients with psoriasis in routine clinical practice. In this multicenter, observational, open-label, postmarketing study, primary efficacy measures included the Psoriasis Area and Severity Index ( PASI) and the Dermatology Life Quality Index ( DLQI) in all patients with psoriasis. In patients with psoriatic arthritis (PsA), the 28-joint Disease Activity Score ( DAS28) and the visual analog scale ( VAS) pain were also evaluated. Safety was assessed based on the frequency of adverse drug reactions ( ADR). Among patients with psoriasis evaluated for efficacy ( n = 604), significant improvements from baseline were observed in mean PASI and DLQI scores at weeks 16 and 24 (all P < 0.0001). Furthermore, in psoriasis patients without PsA, the PASI 75/90 response rates were 55.9%/28.4% at week 16 ( n = 306) and 65.6%/43.3% at week 24 ( n = 270), respectively. In patients with PsA evaluable for effectiveness, significant improvements from baseline were observed in PASI, DAS28 erythrocyte sedimentation rate, DAS28 C-reactive protein and VAS pain at weeks 16 and 24 (all P < 0.0001). ADR and serious ADR were reported by 26.1% and 3.3%, respectively, of 731 safety evaluable patients with psoriasis; no unexpected safety findings were noted. The safety profile and effectiveness of adalimumab for the treatment of psoriasis in a routine clinical setting were as expected in Japanese patients. [ABSTRACT FROM AUTHOR]

Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis and psoriatic arthritis. Japanese patients aged 20 years or more with moderate to severe plaque psoriasis and/or psoriatic arthritis were double-blindly randomized 1:1 to tofacitinib 5 or 10 mg b.i.d. for 16 weeks, open-label 10 mg b.i.d. for 4 weeks, then variable 5 or 10 mg b.i.d. to Week 52. Primary end-points at Week 16 were the proportion of patients achieving at least a 75% reduction in Psoriasis Area and Severity Index ( PASI75) and Physician's Global Assessment of 'clear' or 'almost clear' ( PGA response) for psoriasis, and 20% or more improvement in American College of Rheumatology criteria ( ACR20) for patients with psoriatic arthritis. Safety was assessed throughout. Eighty-seven patients met eligibility criteria for moderate to severe plaque psoriasis (5 mg b.i.d., n = 43; 10 mg b.i.d., n = 44), 12 met eligibility criteria for psoriatic arthritis (5 mg b.i.d., n = 4; 10 mg b.i.d., n = 8) including five who met both criteria (10 mg b.i.d.). At Week 16, 62.8% and 72.7% of patients achieved PASI75 with tofacitinib 5 and 10 mg b.i.d., respectively; 67.4% and 68.2% achieved PGA responses; all patients with psoriatic arthritis achieved ACR20. Responses were maintained through Week 52. Adverse events occurred in 83% of patients through Week 52, including four (4.3%) serious adverse events and three (3.2%) serious infections (all herpes zoster). No malignancies, cardiovascular events or deaths occurred. Tofacitinib (both doses) demonstrated efficacy in patients with moderate to severe plaque psoriasis and/or psoriatic arthritis through 52 weeks; safety findings were generally consistent with prior studies. [ABSTRACT FROM AUTHOR]

Psoriasis has been shown to accompany systemic inflammation. We aimed to examine serum C-reactive protein ( CRP) levels in Japanese psoriatic patients, and to elucidate their long-term as well as short-term changes by treatment with different biologics. A retrospective study was conducted in those who initiated and successfully continued the treatment for up to 24 months with either infliximab, adalimumab or ustekinumab, at the psoriasis special clinic of Jikei University School of Medicine. A total of 212 patients were included, 171 with plaque-type psoriasis (PsV) and 41 with psoriatic arthritis (PsA). A statistically significant elevation of CRP values was found in the group with a Psoriasis Area and Severity Index ( PASI) of 12 or more compared with the PASI of less than 12 for both PsV and PsA. The CRP-positive patients had a higher proportion of PsA compared with the CRP-negative patients, and they had significantly higher PASI scores. Serum CRP values declined as early as at 3 months after systemic treatment with biologics. Tumor necrosis factor ( TNF)-α antagonists did lead to a notable and sustained CRP decline up to 24 months. Infliximab showed rapid decline, while CRP decline by adalimumab treatment was time-dependent. The interleukin-12/23 p40 antagonist, ustekinumab, appeared to be less potent than TNF-α antagonists in stabilizing CRP values at low levels despite good control of cutaneous lesions. In conclusion, serum CRP levels can be used to assess disease severity in Japanese psoriatic patients as a marker of systemic inflammation. TNF-α antagonists may be more beneficial than ustekinumab in this regard. [ABSTRACT FROM AUTHOR]