Neutrophilic panniculitis associated with alpha-1-antitrypsin deficiency: an update

• Published in: British journal of dermatology (1951) Vol. 174; no. 4; pp. 753 - 762
• Main Authors: Blanco, I., Lipsker, D., Lara, B., Janciauskiene, S.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2016
• Subjects: Adolescent; Adult; alpha 1-Antitrypsin - physiology; alpha 1-Antitrypsin Deficiency - complications; alpha 1-Antitrypsin Deficiency - pathology; Female; Humans; Male; Middle Aged; Neutrophils; Panniculitis - etiology; Panniculitis - pathology; Young Adult
• ISSN: 0007-0963; 1365-2133; 1365-2133
• DOI: 10.1111/bjd.14309

Summary Neutrophilic panniculitis associated with alpha‐1‐antitrypsin deficiency (AATD) is a very rare disease. Its estimated prevalence is 1 in 1000 subjects with severe AATD (usually white individuals with a Pi*ZZ genotype). It is manifested clinically by painful recurrent ulcerating subcutaneous nodules, and characterized histologically by dense infiltrates of neutrophils in the deep dermis and connective‐tissue septae, with secondary lobular panniculitis. It may be the only clinical manifestation of AATD, although it can also occur together with the classical pulmonary or hepatic manifestations of the disease. AATD‐associated panniculitis is not only very rare but may also be significantly underdiagnosed. The physician managing a case of panniculitis with a clinical presentation suggestive of AATD and a compatible skin biopsy should measure serum AAT concentration and, if low, determine the AAT phenotype by isoelectric focusing. If uncertainty remains, the SERPINA1 gene should be sequenced to identify the genotype. If AATD is diagnosed, AATD testing of first‐degree family members should be performed in order to take appropriate preventive and therapeutic measures, including genetic counselling, education on inheritance, risk arising from tobacco smoke, occupational exposure to pollutants and hepatotoxic substances, and the provision of information on clinical management. Cases of panniculitis in which conventional therapy with dapsone has failed may be managed with intravenous augmentative therapy using human AAT. The current manuscript addresses the fundamental concepts of the pathogenesis of AATD‐associated panniculitis and describes the clinical presentation and management of cases in order to reduce underdiagnosis and improve outcomes. What's already known about this topic? Panniculitis associated with alpha‐1‐antitrypsin (AAT) deficiency is a rare disease generally associated with Pi*ZZ genotypes. Important clinical, epidemiological, pathogenic and therapeutic aspects remain as yet unknown. What does this study add? To make a firm diagnosis, a deep‐skin biopsy complemented with blood AAT measurement and Pi‐AAT phenotype–genotype characterization is required. Although dapsone is currently the drug of choice for initiating an empirical treatment, studies to establish a pharmacological regimen based on scientific evidence are still needed. Linked Comment: Cardoso. Br J Dermatol 2016; 174:711–712.