Summary
Background
The infection caused by the recently identified SARS‐CoV‐2, called coronavirus disease‐19 (COVID‐19), has rapidly spread throughout the world. With the exponential increase of ...patients worldwide, the clinical spectrum of COVID‐19 is being better defined and new symptoms are emerging. Numerous reports are documenting the occurrence of different cutaneous manifestations in patients with COVID‐19.
Objectives
To provide a brief overview of cutaneous lesions associated with COVID‐19.
Methods
A literature search was performed in the PubMed, Scopus and Web of Science databases up to 30 April 2020. This narrative review summarizes the available data regarding the clinical and histological features of COVID‐19‐associated skin manifestations.
Results
The literature reports showed a great heterogeneity in COVID‐19‐associated cutaneous manifestations, as well as in their latency periods and associated extracutaneous symptoms. Pathogenic mechanisms are unknown, although the roles of a hyperactive immune response, complement activation and microvascular injury have been hypothesized. Based on our experience and the literature data, we subdivided the reported cutaneous lesions into six main clinical patterns: (i) urticarial rash; (ii) confluent erythematous–maculopapular–morbilliform rash; (iii) papulovesicular exanthem; (iv) chilblain‐like acral pattern; (v) livedo reticularis–livedo racemosa‐like pattern; and (vi) purpuric ‘vasculitic’ pattern. These six patterns can be merged into two main groups: the first – inflammatory and exanthematous – includes the first three groups listed above, and the second includes the vasculopathic and vasculitic lesions of the last three groups.
Conclusions
The possible presence of cutaneous findings leading to suspect COVID‐19 puts dermatologists in a relevant position. Further studies are needed to delineate the diagnostic and prognostic values of such cutaneous manifestations.
What is already known about this topic?
The infection caused by the SARS‐CoV‐2, called coronavirus disease‐19 (COVID‐19), has rapidly spread throughout the world, becoming pandemic.
The heterogeneous spectrum of COVID‐19‐associated cutaneous manifestations is based on preliminary reports of different types of skin lesions, leading to a need for clarity.
What does this study add?
A summary of the clinical and histological features of COVID‐19‐associated skin manifestations is provided.
Six main clinical patterns can be identified: (i) urticarial rash; (ii) confluent erythematous–maculopapular–morbilliform rash; (iii) papulovesicular exanthem; (iv) chilblain‐like acral pattern; (v) livedo reticularis–livedo racemosa‐like pattern; and (vi) purpuric ‘vasculitic’ pattern.
Plain language summary available online
This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and ...patient organizations. It is a S3 consensus‐based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue‐bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10–25% of patients laminin 332 is recognized. In 25–30% of MMP patients with anti‐laminin 332 reactivity, malignancies have been associated. As first‐line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first‐line regimens. Additional recommendations are given, tailored to treatment of single‐site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high‐quality randomized controlled trials.
Background
Chronic spontaneous urticaria (CSU) is defined as spontaneous occurrence of wheals and/or angioedema for ≥6 weeks. Omalizumab is a monoclonal anti‐IgE antibody effective in refractory CSU, ...but its mechanism of action and markers predictive of response remain not completely defined.
Objectives
To correlate baseline levels of two proposed biomarkers, total IgE (bIgE) and d‐dimer (bd‐dimer), and clinical parameters to omalizumab response and to relapses after drug withdrawal.
Methods
In this retrospective Italian multicentre study, clinical data were collected in 470 CSU patients, and bIgE and bd‐dimer were measured in 340 and 342 patients, respectively. Disease activity was determined by Urticaria Activity Score 7 (UAS7) at week 1 and 12 after omalizumab starting. Relapses were evaluated during a 2‐ and 3‐month interval after a first and a second course of treatment, respectively.
Results
bIgE correlated to a good response to omalizumab since levels were significantly higher in responders than non‐responders (P = 0.0002). Conversely, bd‐dimer did not correlate to response. There was no correlation between both bIgE and d‐dimer and either first or second relapse. Disease duration was significantly longer in patients who experienced either first or second relapse (P < 0.0001 and P = 0.0105, respectively), while baseline UAS7 correlated only to first relapse (P = 0.0023).
Conclusions
Our study confirms bIgE as a reliable biomarker predicting response to omalizumab in CSU, while it does not support the usefulness of bd‐dimer unlike previous findings. CSU duration before omalizumab and baseline UAS7 may be clinical markers of relapse risk.
This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a ...contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus‐based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono‐ or multisite involvement. Patients’ autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the ‘Cicatrising Conjunctivitis Assessment Tool’ and the Oral Disease Severity Score (ODSS). Patient‐reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course.
By analyzing the exomes of 12,332 unrelated Swedish individuals, including 4,877 individuals affected with schizophrenia, in ways informed by exome sequences from 45,376 other individuals, we ...identified 244,246 coding-sequence and splice-site ultra-rare variants (URVs) that were unique to individual Swedes. We found that gene-disruptive and putatively protein-damaging URVs (but not synonymous URVs) were more abundant among individuals with schizophrenia than among controls (P = 1.3 × 10
). This elevation of protein-compromising URVs was several times larger than an analogously elevated rate for de novo mutations, suggesting that most rare-variant effects on schizophrenia risk are inherited. Among individuals with schizophrenia, the elevated frequency of protein-compromising URVs was concentrated in brain-expressed genes, particularly in neuronally expressed genes; most of this elevation arose from large sets of genes whose RNAs have been found to interact with synaptically localized proteins. Our results suggest that synaptic dysfunction may mediate a large fraction of strong, individually rare genetic influences on schizophrenia risk.
Summary
Background
The anti‐tumour necrosis factor (TNF)‐α adalimumab is the only licenced biologic for moderate‐to‐severe hidradenitis suppurativa (HS). No predictors of response have been ...identified so far.
Objectives
To identify clinical parameters predicting response to adalimumab and confirm its efficacy/safety.
Methods
The data of 389 patients with HS treated with adalimumab in 21 Italian centres were reviewed. Sex, age at onset/diagnosis/baseline, body mass index, smoking, phenotype, previous treatments, concomitant antibiotics and ‘therapeutic delay’, defined as the time from HS onset to adalimumab initiation, were assessed. Response to adalimumab and its impact on quality of life (QoL) were evaluated using the Hidradenitis Suppurativa Clinical Response (HiSCR) and the Dermatology Life Quality Index (DLQI) or the Visual Analogue Scale for pain (VAS pain), respectively. Logistic regression analysis was performed.
Results
The therapeutic delay correlated to lack of response to adalimumab at week 16 odds ratio (OR) 1·92 for therapeutic delay > 10 years; 95% confidence interval (CI) 1·28–2·89; P = 0·0016). HiSCR was achieved in 43·7% and 53·9% patients at week 16 and 52, respectively. Significant reductions in both DLQI and VAS pain were found between week 16 vs. baseline (P < 0·0001 for both) and week 52 vs. baseline (P < 0·0001 for both). Previous immunosuppressants inversely correlated to HiSCR at week 52 (OR = 1·74, 95% CI 1·04–2·91, P = 0·0342).
Conclusions
Inverse correlation between therapeutic delay and clinical response was found, supporting early adalimumab use and providing evidence for a ‘window of opportunity’ in HS treatment. Adalimumab efficacy and safety were confirmed, along with patients’ QoL improvement. Immunosuppressants could negatively influence the response to adalimumab inducing a switch to non‐TNF‐α‐driven pathways.
What is already known about this topic?
Adalimumab is an effective and safe biologic licenced for the treatment of moderate‐to-severe hidradenitis suppurativa (HS) after failure of conventional treatments.
There are no reliable parameters that predict the clinical response to adalimumab in this disease.
What does this study add?
The therapeutic delay, defined as the time from HS onset to adalimumab initiation, significantly correlated to lack of clinical response to this drug, particularly at week 16 of treatment.
This study suggests that using adalimumab in the early phases of HS should be highly encouraged.
Linked Comment: Zouboulis. Br J Dermatol 2021; 184:10–11.
Plain language summary available online
Large (>100 kb), rare (<1% in the population) copy number variants (CNVs) have been shown to confer risk for schizophrenia (SZ), but the findings for bipolar disorder (BD) are less clear. In a new BD ...sample from the United Kingdom (n=2591), we have examined the occurrence of CNVs and compared this with previously reported samples of 6882 SZ and 8842 control subjects. When combined with previous data, we find evidence for a contribution to BD for three SZ-associated CNV loci: duplications at 1q21.1 (P=0.022), deletions at 3q29 (P=0.03) and duplications at 16p11.2 (P=2.3 × 10(-4)). The latter survives multiple-testing correction for the number of recurrent large CNV loci in the genome. Genes in 20 regions (total of 55 genes) were enriched for rare exonic CNVs among BD cases, but none of these survives correction for multiple testing. Finally, our data provide strong support for the hypothesis of a lesser contribution of very large (>500 kb) CNVs in BD compared with SZ, most notably for deletions >1 Mb (P=9 × 10(-4)).
Multiple nodules on the scrotal wall Giacalone, S.; Genovese, G.; Cusini, M.
Clinical and experimental dermatology,
December 2021, Letnik:
46, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Click https://wileyhealthlearning.com/#/online-courses/524c0ff4-4240-4ed9-a57f-c7a4eb6fe0fc for the corresponding questions to this CME article.
SAPHO syndrome, namely Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis, is a rare autoinflammatory chronic disease presenting with non‐infectious inflammatory osteitis, sterile joint ...inflammation and skin manifestations, including palmoplantar pustulosis and severe acne. The case of a 15‐year‐old boy affected by SAPHO syndrome and hidradenitis suppurativa (HS) is presented and discussed. Coexistence of these two diseases may represent a therapeutic challenge and this case confirms literature data reporting the efficacy of the combination of methotrexate and adalimumab in SAPHO complicated by HS.
PDF
