Background Omalizumab, a recombinant anti-IgE antibody, effectively treats chronic spontaneous urticaria. Evidence is lacking in patients with chronic inducible urticarias (CIndUs), which are frequently H 1 -antihistamine resistant. Objective From the current published literature, we aimed to determine the strength of evidence for omalizumab efficacy and safety in the treatment of CIndUs. Methods We performed a PubMed search to identify evidence on omalizumab use in the following 9 CIndU subtypes: symptomatic dermographism, cold urticaria, delayed-pressure urticaria, solar urticaria, heat urticaria, vibratory angioedema, cholinergic urticaria, contact urticaria, and aquagenic urticaria. Results Forty-three trials, case studies, case reports, and analyses were identified. Our review indicates that omalizumab has substantial benefits in patients with various CIndUs. The evidence is strongest for symptomatic dermographism, cold urticaria, and solar urticaria. Little/no evidence was available on vibratory angioedema and aquagenic and contact urticaria. Our review supports rapid onset of action demonstrated through early symptom control in most cases, sometimes within 24 hours. Many patients gained complete/partial symptom relief and substantially improved quality of life. Adverse events were generally low, with omalizumab being well tolerated by most patients, including children. Conclusions A strong body of evidence supports the use of omalizumab in the treatment of patients with therapy-refractory CIndU. More data from randomized controlled studies are warranted.

Omalizumab treatment in patients with chronic inducible urticaria: A systematic review of published evidence

Scleroderma refers to an autoimmune connective tissue fibrosing disease, including three different subsets: localized scleroderma, limited cutaneous systemic sclerosis, and diffuse cutaneous systemic sclerosis with divergent patterns of organ involvement, autoantibody profiles, management, and prognostic implications. Although systemic sclerosis is considered the disease prototype that causes cutaneous sclerosis, there are many other conditions that can mimic and be confused with SSc. They can be classified into immune-mediated/inflammatory, immune-mediated/inflammatory with abnormal deposit (mucinoses), genetic, drug-induced and toxic, metabolic, panniculitis/vascular, and (para)neoplastic disorders according to clinico-pathological and pathogenetic correlations. This article reviews the clinical presentation with emphasis on cutaneous disease, etiopathogenesis, diagnosis, and treatment options available for the different forms of scleroderma firstly and for scleroderma-like disorders, including scleromyxedema, scleredema, nephrogenic systemic fibrosis, eosinophilic fasciitis, chronic graft-versus-host disease, porphyria cutanea tarda, diabetic stiff-hand syndrome (diabetic cheiroartropathy), and other minor forms. This latter group of conditions, termed also scleroderma mimics, sclerodermiform diseases, or pseudosclerodermas, shares the common thread of skin thickening but presents with distinct cutaneous manifestations, skin histology, and systemic implications or disease associations, differentiating each entity from the others and from scleroderma. The lack of Raynaud's phenomenon, capillaroscopic abnormalities, or scleroderma-specific autoantibodies is also important diagnostic clues. As cutaneous involvement is the earliest, most frequent and characteristic manifestation of scleroderma and sclerodermoid disorders, dermatologists are often the first-line doctors who must be able to promptly recognize skin symptoms to provide the affected patient a correct diagnosis and appropriate management.

Cutaneous Manifestations of Scleroderma and Scleroderma-Like Disorders: a Comprehensive Review

The efficient healing of skin wounds is crucial for securing the vital barrier function of the skin, but pathological wound healing and scar formation are major medical problems causing both physiological and psychological challenges for patients. A number of tightly coordinated regenerative responses, including haemostasis, the migration of various cell types into the wound, inflammation, angiogenesis, and the formation of the extracellular matrix, are involved in the healing process. In this article, we summarise the central mechanisms and processes in excessive scarring and acute wound healing, which can lead to the formation of keloids or hypertrophic scars, the two types of fibrotic scars caused by burns or other traumas resulting in significant functional or aesthetic disadvantages. In addition, we discuss recent developments related to the functions of activated fibroblasts, the extracellular matrix and mechanical forces in the wound environment as well as the mechanisms of scarless wound healing. Understanding the different mechanisms of wound healing is pivotal for developing new therapies to prevent the fibrotic scarring of large skin wounds.

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Toward understanding scarless skin wound healing and pathological scarring.

Importance Omalizumab is indicated for the management of chronic idiopathic urticaria (CIU) (also known as chronic spontaneous urticaria) in adolescents and adults with persistent hives not controlled with antihistamines. The effectiveness of omalizumab in the real-world management of CIU is largely unknown. Objective To quantitatively synthesize what is known about the benefits and harms of omalizumab in the real-world clinical management of CIU regarding urticaria activity, treatment response, and adverse events. Data Sources Published observational studies (January 1, 2006, to January 1, 2018) and scientific abstracts on the effectiveness of omalizumab in CIU were identified using PubMed, Embase, Web of Science, and Cochrane search engines; references were searched to identify additional studies. Study Selection Included studies were observational in design and included at least 1 outcome in common with other studies and at a concurrent time point of exposure to omalizumab. A total of 67 articles (35.2% of those screened) were included in the analysis. Data Extraction and Synthesis PRISMA and MOOSE guidelines were followed; independent selection and data extraction were completed by 2 observers. Random-effects meta-analyses were performed. Main Outcomes and Measures Main outcomes were change in weekly Urticaria Activity Score (UAS7; range, 0-42), change in Urticaria Activity Score (UAS; range 0-6) (higher score indicating worse outcome in both scales), complete and partial response rates (percentages), and adverse event rate (percentage). Results Omalizumab therapy was associated with an improvement in UAS7 scores (−25.6 points, 95% CI, −28.2 to −23.0;P  Conclusions and Relevance Benefits and safety of omalizumab in the real-world treatment of CIU meet or exceed results gleaned from clinical trials. These real-world data on omalizumab in CIU may help inform both clinical treatment expectations and policy decision making.

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Benefits and Harms of Omalizumab Treatment in Adolescent and Adult Patients With Chronic Idiopathic (Spontaneous) Urticaria: A Meta-analysis of “Real-world” Evidence

Importance Chronic urticaria (CU) affects 0.1% to 0.3% of children. Most cases have no identifiable trigger and are classified as chronic spontaneous urticaria (CSU). At least half of patients with CSU may have an autoimmune etiology that can be determined in vitro using the basophil activation test (BAT). While 30% to 55% of CU cases resolve spontaneously within 5 years in adults, the natural history and predictors of resolution in children are not known. Objective To assess the comorbidities, natural history of CU, and its subtypes in children and identify predictors of resolution. Design, Setting, and Participants We followed a pediatric cohort with chronic urticaria that presented with hives lasting at least 6 weeks between 2013 and 2015 at a single tertiary care referral center. Exposures Data were collected on disease activity, comorbidities, physical triggers, BAT results, complete blood cell count, C-reactive protein levels, thyroid-stimulating hormone levels, and thyroid peroxidase antibodies. Main Outcomes and Measures We assessed the rate of resolution (defined as absence of hives for at least 1 year with no treatment) and the association with clinical and laboratory markers. Results The cohort comprised 139 children younger than 18 years old. Thirty-one patients (20%) had inducible urticaria, most commonly cold induced. Six children had autoimmune comorbidity, such as thyroiditis and type 1 diabetes. Autoimmune disorders (24 patients [17%]) and CU (17 patients [12%]) were common in family members. Positive BAT results (CD63 levels > 1.8%) were found in 58% of patients. Patients with positive BAT results (CD63 level >1.8%) were twice as likely to resolve after 1 year compared with negative BAT results (hazard ratio [HR], 2.33; 95% CI, 1.08-5.05). In contrast, presence of basophils decreased the likelihood of resolution (HR, 0.40; 95% CI, 0.20-0.99). No correlation with age was found. Chronic urticaria resolved in 43 patients, with a rate of resolution of 10.3% per year. Levels of CD63 higher than 1.8% and absence of basophils were associated with earlier disease resolution. Conclusions and Relevance Resolution rate in children with CU is low. The presence of certain biomarkers (positive BAT result and basophil count) may help to predict the likelihood of resolution.

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Evaluating Comorbidities, Natural History, and Predictors of Early Resolution in a Cohort of Children With Chronic Urticaria

GENERAL PURPOSE:To provide information about the clinical presentation of hypertrophic scars and keloids based on their varied structural components.TARGET AUDIENCE:This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest i

Insights into the Pathophysiology of Hypertrophic Scars and Keloids: How Do They Differ?

anti-IgE antibody (omalizumab) could contribute to a new therapeutic scenario for SU and throw light on the potential pharmacological mechanism of omalizumab in this disease. In fact, it is conceivable that omalizumab, depleting IgE, downregulates mast cell activities and reduces mast cell-dependent inflammatory mechanisms (8). Further studies are needed to identify patients with SU who could be treated earlier and successfully with omalizumab. In addition, randomized controlled trials are awaited to identify both effective treatment schedule(s) and doses for eligible patient suffering from solar urticaria unresponsive to conventional treatment.

Management of pediatric chronic spontaneous and physical urticaria patients with omalizumab: case series

A 51-year-old man presented with a 6-month history of asymptomatic eruptive skin-coloured lesions in his groin ([Figure 1][1]). He did not report any high-risk sexual behaviour leading up to development of the lesions. He had received a kidney transplant 3 years earlier and was taking a number of

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Eruptive syringomas in the groin.

Merkel cell carcinoma (MCC) is an aggressive tumor of the skin and mucous membranes that typically occurs in elderly white men and in immunosuppressed individuals. The reported incidence of MCC has tripled over the last 20 years in the United States1 from 0.15 to 0.44 cases per 100 000 between 1986 and 2001.2 In light of the poor prognosis and high risk for recurrence, metastasis, and death associated with MCC, this increasing trend is of concern. The risk factors for MCC are similar to those for other skin cancers, mainly ultraviolet light exposure, older age, T-cell immunosuppression, fair skin, and male sex.3, 4 Although a rare tumor, MCC is seen more frequently in the immunosuppressed population, and immunosuppressed MCC patients tend to be younger at diagnosis and have less favorable disease outcomes. Specifically, HIV positivity,1 lymphocytic leukemia,2 and iatrogenic immunosuppression after organ transplantation3 confer an increased risk of MCC.

Here we report 2 cases of MCC occurring in organ transplant recipients (OTRs), illustrating how iatrogenic immunosuppression in the setting of organ transplantation can impact tumor progression and potentially decrease survival. We summarize current evidence regarding the pathogenesis, staging, and treatment of MCC and bring forth our recommendation to monitor high-risk OTR with frequent skin examinations. MCC has a poor prognosis and its management remains a challenge. Early recognition can improve clinical outcomes and disease-specific and overall survival in the transplant population.

https://www.jaadcasereports.org/article/S2352-5126(15)00160-5/pdf

Merkel cell carcinoma in organ transplant recipients: Case reports and review of the literature

Linear atrophoderma of Moulin (LAM) is an acquired skin condition that manifests in early childhood and adolescence. It likely represents a form of cutaneous mosaicism that presents with linear, hyperpigmented and atrophic lesions appearing on the trunk and limbs. Its clinical appearance varies and may closely resemble that of atrophoderma of Pasini and Pierini (APP) and linear scleroderma. LAM usually follows a benign course and no effective treatment options exist. We present a case of a young and healthy patient that developed such lesions on her upper and lower extremities over 5 years. The initial clinical impression of linear scleroderma was reviewed in favor of LAM following histological examination of the lesions which revealed no significant inflammatory changes. LAM remains a rare and possibly under recognized entity with reports confined only to the dermatologic literature. This case highlights the importance of recognizing LAM and distinguishing it from linear scleroderma given the significant differences in management and prognosis.

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Fatemeh Jafarian

Papers

Insights into the Pathophysiology of Hypertrophic Scars and Keloids: How Do They Differ?

Management of pediatric chronic spontaneous and physical urticaria patients with omalizumab: case series

Eruptive syringomas in the groin.

Merkel cell carcinoma in organ transplant recipients: Case reports and review of the literature

Linear atrophoderma of Moulin: an underrecognized entity