New Findings in PiZZ α&lt;sub&gt;1&lt;/sub&gt;-Antitrypsin Deficiency-Related Panniculitis

Gross, Bettina; Grebe, Mathias; Wencker, Marion; Stoller, James K.; Bjursten, Lars Magnus; Janciauskiene, Sabina

doi:10.1159/000202982

Cited by 67 publications

(26 citation statements)

References 54 publications

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“…Alpha‐1 antitrypsin is a glycoprotein that is an acute phase reactant (2). It is mainly synthesized in the liver and to a small extent in the lung (2,3). It is one of the most abundant serine protease inhibitors in humans; it regulates a wide array of proteolytic enzymes including elastase, chymotrypsin, and trypsin (3–5).…”

Section: Introductionmentioning

confidence: 99%

“…Notably, less than 10% have been diagnosed (7,8). Alpha‐1 antitrypsin deficiency is inherited as an autosomal co‐dominant disorder (2,3,8). More than 100 alleles of alpha‐1 antitrypsin have been identified (3).…”

Section: Introductionmentioning

confidence: 99%

“…Alpha‐1 antitrypsin deficiency is inherited as an autosomal co‐dominant disorder (2,3,8). More than 100 alleles of alpha‐1 antitrypsin have been identified (3). The phenotypes are classified based on the speed they migrate on gel electrophoresis: M = medium, S = slow, and Z = very slow (2–4).…”

Section: Introductionmentioning

confidence: 99%

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Metabolic panniculitis: alpha-1 antitrypsin deficiency panniculitis and pancreatic panniculitis

Lyon

2010

Dermatologic Therapy

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Panniculitis can be the initial presentation of both alpha-1 antitrypsin deficiency and pancreatic disease. They can both present with abscess-like draining nodules, but may present like other forms of panniculitis with erythematous nodules. It is important to consider these in the differential diagnosis of patients presenting with panniculitis. Alpha-1 antitrypsin deficiency is a relatively common disorder mainly affecting the lungs and liver. It frequently goes undiagnosed, yet critical interventions can be made to minimize disease progression. Panniculitis associated with alpha-1 antitrypsin deficiency can be difficult to treat. Pancreatic panniculitis occurs in less than 3% of patients with underlying pancreatic disease and is often associated with arthritis. Diagnosis and treatment of the underlying pancreatic disease is imperative.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metabolic panniculitis: alpha-1 antitrypsin deficiency panniculitis and pancreatic panniculitis

Lyon

2010

Dermatologic Therapy

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“…1 Cigarette smoking is a major risk factor that accelerates the pulmonary complications associated with this condition. In addition, patients may also develop liver disease (chronic hepatitis, cirrhosis and hepatocellular carcinoma), which can present as early as childhood, 2 and other less common disorders such as panniculitis 3 and vasculitis. 4 As diseases associated with AATD are progressive, early diagnosis is key in order to initiate proactive interventions to minimize pulmonary complications, such as smoking cessation and treatment with intravenous (IV) infusions of donor-derived purified human AAT to slow the progression of emphysema.…”

Section: Introductionmentioning

confidence: 99%

<p>New Patient-Centric Approaches to the Management of Alpha-1 Antitrypsin Deficiency</p>

Chorostowska‐Wynimko¹,

Barrecheguren²,

Ferrarotti³

et al. 2020

COPD

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Alpha-1 antitrypsin deficiency (AATD) is a rare and underdiagnosed genetic predisposition for COPD and emphysema and other conditions, including liver disease. Although there have been improvements in terms of awareness of AATD and understanding of its treatment in recent years, current challenges center on optimizing detection and management of patients with AATD, and improving access to intravenous (IV) AAT therapythe only available pharmacological intervention that can slow disease progression. However, as an orphan disease with geographically dispersed patients, international cooperation is essential to address these issues. To achieve this, new European initiatives in the form of the European Reference Network for Rare Lung Diseases (ERN-LUNG) and the European Alpha-1 Research Collaboration (EARCO) have been established. These organizations are striving to address the current challenges in AATD, and provide a new platform for future research efforts in AATD. The first objectives of ERN-LUNG are to establish a quality control program for European AATD laboratories and create a disease management program for AATD, following the success of such programs in the United States. The main purpose of EARCO is to create a pan-European registry, with the aim of understanding the natural history of the disease and supporting the development of new treatment modalities in AATD and access to AAT therapy. Going further, other patient-centric initiatives involve improving the convenience of intravenous AAT therapy infusions through extended-interval dosing and self-administration. The present review will discuss the implementation of these initiatives and their potential contribution to the optimization of patient care in AATD.

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“…The lesions of panniculitis contain neutrophils that co-localize with polymers, though normal skin of the Z α 1 -antitrypsin homozygote also contains polymers 31. It remains to be seen whether polymers are simply an incidental finding, or whether they play a role in the pathogenesis of the disease.…”

Section: Introductionmentioning

confidence: 99%

Why has it been so difficult to prove the efficacy of alpha-1-antitrypsin replacement therapy? Insights from the study of disease pathogenesis

Dickens

Lomas²

2011

DDDT

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Alpha-1-antitrypsin is the most abundant circulating protease inhibitor. It is mainly produced by the liver and secreted into the circulation where it acts to prevent excessive proteolytic damage in the lungs by the enzyme neutrophil elastase. The most common severe deficiency allele is the Z mutation, which causes the protein to self-associate into ordered polymers. These polymers accumulate within hepatocytes to cause liver damage. The resulting lack of circulating α1-antitrypsin predisposes the Z homozygote to proteolytic lung damage and emphysema. Other pathways may also contribute to the development of lung disease. In particular, polymers of Z α1-antitrypsin can form within the lung where they act as a pro-inflammatory stimulus that may exacerbate protease-mediated lung damage. Researchers recognized in the 1980s that plasma α1-antitrypsin levels could be restored by intravenous infusions of purified human protein. Alpha-1-antitrypsin replacement therapy was introduced in 1987 but subsequent clinical trials have produced conflicting results, and to date there remains no widely accepted clinical evidence of the efficacy of α1-antitrypsin replacement therapy. This review addresses our current understanding of disease pathogenesis in α1-antitrypsin deficiency and questions why this treatment in isolation may not be effective. In particular it discusses the possible role of α1-antitrypsin polymers in exacerbating intrapulmonary inflammation and attenuating the efficacy of α1-antitrypsin replacement therapy.

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New Findings in PiZZ α<sub>1</sub>-Antitrypsin Deficiency-Related Panniculitis

Cited by 67 publications

References 54 publications

Metabolic panniculitis: alpha-1 antitrypsin deficiency panniculitis and pancreatic panniculitis

Metabolic panniculitis: alpha-1 antitrypsin deficiency panniculitis and pancreatic panniculitis

<p>New Patient-Centric Approaches to the Management of Alpha-1 Antitrypsin Deficiency</p>

Why has it been so difficult to prove the efficacy of alpha-1-antitrypsin replacement therapy? Insights from the study of disease pathogenesis

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