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

Abstract

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.

Alpha‐1 antitrypsin deficiency panniculitis: clinical and pathologic characteristics of 10 cases

“…Lack or dysfunction of AAT leads to unchecked neutrophil elastase and other proteases, causing elastolysis and tissue destruction. It has been postulated that panniculitis arises as a result of excessive protease and lipase activity not neutralized by AAT, released into subcutaneous tissue from local cells …”

“…The other pulmonary findings and arthritis in this cohort are likely unrelated to AATD. A lack of typical AATD‐associated disease findings was also noted in a recent report by Blanco, et al ., who summarized 13 cases of patients with AATD panniculitis with only one of 13 cases having associated emphysema . The tertiary referral and consultative nature of our practice likely limited our availability to assess associated systemic symptoms as only four patients had pulmonary function testing performed at our institution.…”

“…Panniculitis associated with AATD is extremely rare, with fewer than 50 cases reported in the literature . The disease presentation is classically described as recurrent erythematous subcutaneous nodules on the trunk and proximal extremities that frequently develop discrete or “punched‐out” ulcers draining a characteristic oily material and heal with atrophic scarring .…”

Can Alpha-1 Antitrypsin be Involved in the Carcinogenesis of Colorectal Cancer?

“…Consequently, the vast majority of genotypes result from combinations of M, S and Z, that is: MM (normal genotype present in about of 85-95% people, expressing 100% of AAT), MS, SS, MZ, SZ and ZZ (five deficiency genotypes present in 5-15% of remaining people, expressing grosso modo 80, 60, 55, 40 and 15% of AAT, respectively [1,2] (Table 1). that predisposes to premature onset of chronic obstructive pulmonary disease (COPD) especially in smokers, liver cirrhosis, neutrophilic panniculitis, systemic vasculitis, and possibly other inflammatory diseases [3,4].…”

The eyelash comes to the fore

“…4 In the past, panniculitis associated with predominantly neutrophilic infiltrates would fall under the rubric Weber-Christian disease, a diagnostic term deemed inadequate by contemporary authors in light of current knowledge, because most cases can be classified within other forms of panniculitis. 5 In 1972, Warter et al published for the first time a case of 'Weber-Christian disease' associated with familial deficiency of AAT.…”