Sporadic late onset nemaline myopathy with concurrent dermatological symptoms responding to immunosuppressive treatment.

BACKGROUND: Sporadic late onset nemaline myopathy is a rare, progressive muscle disease, presenting in adulthood, mainly affecting proximal limb and bulbar muscles. Muscle biopsies show characteristic nemaline rods. The putative mechanism is considered immune-related. Other manifestations aside from neuromuscular symptoms have not been described previously. CASE PRESENTATION: We present a case with atypical sporadic late onset nemaline myopathy (SLONM) of a non-HIV, non-MGUS subtype, where skin manifestations preceded neuromuscular symptoms, and a residual thymus with the histology of thymic follicular hyperplasia was detected during the diagnostic workup. Thorough dermatological investigations could not explain the skin presentations. Muscle biopsy revealed variation in fiber diameter, ragged-red and COX-negative fibers associated with discrete fibrosis. Electron microscopy detected atrophic muscle fibres with disorganization of the myofibrils, nemaline rods and abnormal mitochondria. Single-fiber EMG suggested signs of a neuromuscular transmission defect, EMG showed signs of myopathy. Analyses of antibodies associated with myasthenia gravis were negative. The patient showed improvement after intravenous immunoglobulin treatment regarding both the skin and the muscle symptoms. CONCLUSIONS: Our case highlights the heterogeneity of SLONM with its varied spectrum of presentation. A unique combination of dermatological symptoms and SLONM could be seen with skin lesions as primary presenting symptoms. An association can be considered between the different manifestations, presumably based on immune etiology, where immunosuppressive therapy has been beneficial.

A nationwide 104 weeks real-world study of dupilumab in adults with atopic dermatitis: Ineffectiveness in head-and-neck dermatitis.

BACKGROUND: Evaluation of effectiveness and safety of new systemic treatments for atopic dermatitis (AD) after approval is important. There are few published data exceeding 52-week therapy with dupilumab. OBJECTIVES: To examine the safety, effectiveness and drug survival of dupilumab in a Danish nationwide cohort with moderate-to-severe AD up to 104 weeks exposure. METHODS: We included 347 adult patients with AD who were treated with dupilumab and registered in the SCRATCH registry during 2017-2022. RESULTS: At all visits, we observed improvement in AD severity measured by Eczema Area and Severity Index (EASI) [median (IQR)]. EASI score at baseline was 18.0 (10.6-25.2), at week 4: 6.5 (3.5-11.6), at week 16: 3.7 (1.2-6.2), at week 52: 2.0 (0.8-3.6), at week 104: 1.7 (0.8-3.8). While drug survival was high (week 52: 90%; week 104: 86%), AD in the head-and-neck area remained present in most patients at high levels; proportion with head-and-neck AD at baseline was 76% and 68% at week 104. 35% of patients reported any AE. Conjunctivitis was the most frequent (25% of all patients) and median time to first registration of conjunctivitis was 201 days. CONCLUSIONS: While 2-year drug survival was 86%, dupilumab was unable to effectively treat AD in the head-and-neck area, and conjunctivitis was found in 25% of patients.

Severe and ChRonic Atopic dermatitis Treatment CoHort (SCRATCH): A Danish Real-world Evidence Atopic Dermatitis Treatment Registry.

Data from real-world use of new systemic treatments in atopic dermatitis (AD) is important for assessing safety and efficacy. The aim of this study is to describe the baseline characteristics of adult patients with moderate-to-severe AD enrolled in the Danish nationwide Severe and ChRonic Atopic dermatitis Treatment CoHort (SCRATCH) database, between October 2017 and August 2021. A total of 282 adult patients were included. Most (62%) were men, the median age at baseline was 43 years (interquartile range (IQR) 29-54 years), and median age at onset of AD was 1 year (IQR 0-6 years). The median Eczema Area and Severity Index at treatment initiation was 19.1 (IQR 11.9-25.7); median Patient Oriented Eczema Measure 21.0 (IQR 16.0-25.0); median Dermatology Life Quality Index 13.0 (IQR 7.0-19.0); and median itch and sleep numerical rating scale scores 8.0 (IQR 6.0-9.0) and 6.0 (IQR 4.0-8.0). Differences were found between the sexes. This registry will provide a source for future efficacy and safety studies.

Different Plaque Composition and Progression in Patients with Stable and Unstable Coronary Syndromes Evaluated by Cardiac CT.

OBJECTIVE: To compare the quantity, subtype, and progression of atherosclerosis by cardiac computed tomography (CT) and intravascular ultrasound (IVUS) in patients with stable (SAP) and unstable angina pectoris or non-ST-elevation myocardial infarction (UAP/n-STEMI). METHODS: Forty patients with SAP and 20 with UAP/n-STEMI underwent cardiac CT and angiography with IVUS at baseline and after one year. Atherosclerotic segments were divided into calcified, mixed, or noncalcified subtypes, and significant stenoses were registered. RESULTS: Thirty-two SAP and 15 UAP/n-STEMI patients completed the CT follow-up. At baseline, the number of atherosclerotic segments was higher in UAP/n-STEMI than in SAP (P = 0.039). UAP/n-STEMI patients had more segments with noncalcified plaques (P = 0.0005) whereas SAP patients had more segments with calcified plaques (P = 0.013). The number of segments with significant stenosis did not differ between the groups, but noncalcified plaques more frequently caused significant stenoses in UAP/n-STEMI than in SAP patients (P = 0.0002). After one year the number of segments with atherosclerosis increased in SAP patients (P = 0.0001). The number of atherosclerotic segments remained unchanged in UAP/n-STEMI patients. However, composition was altered as the number of segments with noncalcified plaques decreased (P = 0.018). IVUS data confirmed the CT findings. CONCLUSION: Quantity, subtype, and progression of atherosclerosis differ between SAP and UAP/n-STEMI patients.

Imaging atherosclerotic plaques by cardiac computed tomography in vitro: impact of contrast type and acquisition protocol.

OBJECTIVE: Noninvasive contrast-enhanced coronary computed tomography (CT) angiography enables distinction between calcified and noncalcified atherosclerotic plaques. However, separation of noncalcified plaques into rupture prone lipid-rich and stable fibrous subtypes is challenging because CT density of the plaque, characterized by Hounsfield Units (HU), varies with intraluminal contrast density and acquisition protocol. This study aims at testing the influence of intraluminal contrast densities and kV-settings on coronary plaque density values in vitro. MATERIALS AND METHODS: We scanned 16 coronary arteries with 3 different contrast solutions (no contrast, 1:70, and 1:23 Iomeron, 350 mgI/mL) and 3 different kV-settings (80, 120, and 140 kV). The arteries were sectioned into 5-mm segments. Every segment was evaluated with CT and histopathology for suitability of analysis, presence, and subtype of plaque. RESULTS: Sixty-four segments were analyzed and classified with CT. Agreement between plaques classified with CT angiography in vitro and histopathology was poor-to-moderate, with no kappa-values above 0.21. The kV-settings affected the CT density in all plaque types. The CT density decreased 0.25 (0.07) HU, P=0.013 in noncalcified plaques, and 5.5 (0.7) HU, P<0.0001, in calcified plaques for every kV increase. CT densities in noncalcified plaques changed when the contrast concentration was changed. From no to high contrast concentration resulted in a 21.7 (8.3) HU increase, P=0.041, and from low to high contrast concentration resulted in a 21.5 (6) HU increase, P=0.011, causing several plaques to change in subtype from lipid-rich (low contrast concentration) to fibrotic (high contrast concentration). CONCLUSION: Agreement between CT angiography in vitro and histopathology for classification of coronary plaque subtype is poor to moderate. However, no specific combination seems superior to the most commonly used protocols for distinction between lipid-rich and fibrotic plaque subtypes in current clinical practice.

Impact of luminal density on plaque classification by CT coronary angiography.

UNLABELLED: Non-invasive coronary CT angiography (CCTA) has the potential to characterize the composition of non-calcified coronary plaques. CT-density values characterized by Hounsfield Units (HU) may classify non-calcified plaques as fibrous or lipid-rich, but the luminal density caused by the applied contrast material influences HU in the plaques in vitro. The influence of luminal density on HU in non-calcified plaques in vivo is unknown. Hence the purpose of this study was to test whether plaque characterization by CCTA in vivo depends on luminal density. Two CCTA-scans using two different contrast protocols were obtained from 14 male patients with coronary artery disease. The two contrast protocols applied resulted in high and low luminal density. Eleven non- calcified and 13 calcified plaques were identified and confirmed by intravascular ultrasound. Luminal attenuation differed with the two contrast protocols; 326[284;367] vs. 118[103;134] HU (P < 0.00001). In non-calcified plaques mean HU-values was lower 48[28;69] vs. 11[-4;25] HU (P = 0.004) with the low density protocol. As a consequence three out of eleven non-calcified plaques (27%) were reclassified from fibrous (high) to lipid rich (low). For calcified plaques a less pronounced but still significant difference in HU-values was found with the low luminal density. 770[622;919] vs. 675[496;855] HU (P = 0.02). CONCLUSION: Non-calcified plaques can be identified and classified by CCTA. However, the luminal density affects the absolute HU of both non-calcified and calcified plaques. Characterization and classification of non-calcified plaques by absolute CT values therefore requires standardization of contrast protocols.