Atopic dermatitis (AD) is caused by complex interactions between a variety of genetic and environmental factors that contribute to the maintenance of the chronic inflammatory skin condition. Most ...conventional treatments have been designed for the so-called 'average patient'. In recent years however, many previously unknown details pertaining to the mechanisms of the pathogenesis of AD have been elucidated, and novel treatments based on these pathological mechanisms or on subgroup classifications have been developed. Herein, how future treatment strategies for AD can be developed is described.
OX40 is crucial for T-cell differentiation and memory induction. The anti-OX40 antibody, rocatinlimab inhibits the OX40 pathway. We evaluated the efficacy and safety of rocatinlimab in adults with ...moderate-to-severe atopic dermatitis.
This multicentre, double-blind, placebo-controlled phase 2b study was done at 65 secondary and tertiary sites in the USA, Canada, Japan, and Germany. Eligible patients were adults (aged 18 years or older) with confirmed atopic dermatitis (American Academy of Dermatology Consensus Criteria or local diagnostic criteria) with moderate-to-severe disease activity, as defined by an Eczema Area and Severity Index (EASI) score of 16 or more, validated Investigator's Global Assessment for Atopic Dermatitis score of 3 (moderate) or 4 (severe), and affected body surface area 10% or higher at both screening and baseline, with documented history (within 1 year) of inadequate response to topical medications or if topical treatments were medically inadvisable. Patients were randomly assigned (1:1:1:1:1) to receive subcutaneous rocatinlimab every 4 weeks (150 mg or 600 mg) or every 2 weeks (300 mg or 600 mg) or subcutaneous placebo up to week 18, with an 18-week active-treatment extension and 20-week follow-up. Percentage change from baseline in EASI score was assessed as the primary endpoint at week 16 and during the active extension and follow-up in all randomly assigned patients exposed to study drug with a post-baseline EASI score at week 16 or earlier according to the group they were randomly assigned to. Safety was assessed in all randomly assigned patients exposed to study drug; patients were analysed according to the group they were randomly assigned to. The study is registered with ClinicalTrials.gov, NCT03703102.
Between Oct 22, 2018, and Oct 21, 2019, 274 patients (114 42% women, 160 58% men; mean age 38·0 years SD 14·5) were randomly assigned to one of the rocatinlimab groups (217 79% patients) or to the placebo group (57 21% patients). Compared with placebo (−15·0 95% CI −28·6 to −1·4), significant least-squares mean percent reductions in EASI score at week 16 were observed in all rocatinlimab groups (rocatinlimab 150 mg every 4 weeks −48·3 −62·2 to −34·0, p=0·0003; rocatinlimab 600 mg every 4 weeks −49·7 −64·3 to −35·2, p=0·0002; rocatinlimab 300 mg every 2 weeks −61·1 −75·2 to −47·0, p<0·0001; and rocatinlimab 600 mg every 2 weeks −57·4 −71·3 to −43·4, p<0·0001). The most common adverse events during the double-blind period in patients receiving rocatinlimab (adverse events ≥5% of patients in the total rocatinlimab group and more common than the placebo group) were pyrexia (36 17% patients), nasopharyngitis (30 14% patients), chills (24 11% patients), headache (19 9% patients), aphthous ulcer (15 7% patients), and nausea (13 6% patients). There were no deaths.
Patients treated with rocatinlimab had progressive improvements in atopic dermatitis, which was maintained in most patients after treatment discontinuation. Treatment was well tolerated.
Kyowa Kirin.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The primary symptom of urticarial vasculitis (UV), which is a histopathological leukocytoclastic vasculitis disease, is an eruption that resembles urticaria. Other organs may also experience ...accompanying symptoms. Lung lesions with UV are mostly obstructive pulmonary disease with smoking. However, the coexistence of eosinophilic pneumonia (EP) and complicated UV remains unclear. We report a man in his 70s with chronic obstructive pulmonary disease who attended our department with ring-shaped erythema, marginal edema, and pigmentation. Additionally, a skin histological analysis showed nuclear dust and perivascular neutrophil infiltration, while a blood sample showed a decrease in C3 and C1q concentrations. Administration of prednisone temporarily improved the eruption. However, he developed a cough and a new UV eruption 1 year later. Computed tomography revealed infiltration in the right upper lobe of the lungs, and a blood sample showed a high eosinophil count. He was finally diagnosed with hypocomplementemic urticarial vasculitis syndrome and idiopathic chronic EP. A previous study showed that serum C1q concentrations in patients with EP were lower when this disease was active. Whether a decline in C1q concentrations can cause EP is unclear. However, our case is unique owing to the co-onset of EP with low complement concentrations and recurrence of UV.
Background:
Vascular-type Ehlers–Danlos syndrome (vEDS) is an autosomal dominant inherited disorder caused by a deficit in collagen III as a result of heterogeneous mutations in the α1 type III ...collagen gene (
COL3A1
). Patients with vEDS often experience the first major complications in their early 20s and >80% have at least one complication by their 40s, reducing their average life expectancy to 48 years. Most commonly, vEDS variants are heterozygous missense substitutions of a base-pair encoding a glycine (Gly) residue of the Gly-X-Y repeat of the
COL3A1
protein. When a peptide chain derived from a mutant allele is present in the procollagen triple helical structure, the helical structure cannot be maintained. Therefore, typically, the mutated collagen peptide induces a dominant negative effect on procollagen production. We reported the case of a patient with vEDS and a unique novel duplication mutation without alteration in the Gly-X-Y triplet repeat sequence.
Case presentation:
A 58-year-old man developed a sudden disorder of consciousness and abdominal pain and was consequently taken to a nearby hospital, where an intra-abdominal aneurysm was found, in addition to mild small joint hypermobility and acrogeria. There has been no history of spontaneous pneumothorax, dislocation, or subcutaneous hematoma. The analysis of genomic DNA from a blood sample identified a likely pathogenic in-frame duplication mutation in the
COL3A1
gene coding region. Interestingly, this mutation is not expected to alter the Gly-X-Y triplet repeat sequence. We verified the mutation’s pathogenicity by performing an analysis of synthetic procollagen from cultured skin fibroblasts, electron microscopy, and mRNA expression analysis of unfolded protein response sensors for endoplasmic reticulum (ER) stress.
Conclusion:
Although the clinical findings of the case were mild, when compared to typical vEDS, decreased α1 collagen III levels and morphological abnormalities of the collagenous bundles were observed in the patient samples when compared with the normal control samples. Our evidence supports the conclusion that this variant is pathogenic. However, unlike the common vEDS, ER stress was not observed, and the mild phenotype presentation was suggested to be due to the unique mutation, allowing the triple helical structure to be maintained to a certain extent.
A 47‐year‐old woman with mixed connective tissue disease was treated with abatacept. After 2 months, a 3‐cm depression with atrophied surface was observed on her back, which had histopathological ...consistent with the symptoms of localized scleroderma. Although some cases of paradoxical reaction or cutaneous adverse event have been reported from abatacept, no localized scleroderma has been reported, suggesting this to be a unique case.
In this paper, we bring hope to patients with mycosis fungoides (MF) with CD30+ large‐cell transformation (LCT), which is often a histological marker of poor prognosis and is associated with a mean ...5‐year survival of <20%. Although skin biopsy is a painful procedure, it is the only test for early diagnosis of LCT. Stage IIB has a significantly worse 5‐year survival rate compared with stage IB/IIA, which often plagues clinicians regarding appropriate treatment selection. In this case, the discovery of LCT by skin biopsy prompted treatment with BV. Thus, proactive rebiopsy is important so that CD30+ LCT is not overlooked in the early stage of MF.
Abstract
There have been a few reported cases of erythema nodosum (EN) after coronavirus disease 2019 (COVID‐19) vaccination. A 48‐year‐old healthy woman was referred to our department with multiple ...erythematous nodules of varying sizes on her extremities 10 days after receiving the third COVID‐19 vaccine dose. The clinical and pathological findings of the patients were consistent with EN. We reviewed 18 EN cases post‐COVID‐19 vaccination. Considering the low number of reported EN cases, a causal link between EN and COVID‐19 vaccination is still under debate.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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