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

Abstract

AATD panniculitis should be considered in the differential for a painful, ulcerative panniculitis with a predominantly neutrophilic histopathologic infiltrate. Diagnosis can be made with clinicopathologic correlation and genetic and laboratory evaluations. Serum AAT level and phenotype assists in diagnosing patients with suspected AATD panniculitis.

Alpha-1 antitrypsin deficiency–associated panniculitis

“…17 Only 1 retrospective study of AATD prevalence in panniculitis has been published, 18 describing deficiency in 15 of 96 cases, suggesting significant overpenetration. A follow-up series 19 reported ZZ-AATD in 5 of 10 cases of AATDassociated panniculitis, consistent with previous reports. 10,20 Of the cases reported to date, more than half were the ZZ-genotype, suggesting that AAT levels correlate with risk, although this finding may be affected by acquisition bias.…”

“…56 Lymphocytes (43%), histocytes (37%), and lipophages (27%) were also frequently reported, with eosinophils infrequently reported in the description of histopathologic findings (8%). 18,19,54,[57][58][59] Although secondary leukocytoclastic vasculitis was reported in 9 of 88 (10%) biopsy specimens, primary vasculitis was reported only once. Furthermore, in 1 case showing secondary vasculitis, direct immunofluorescence of tissue showed C3 deposition in the blood vessels of the panniculus and the dermis, with immunoglobulin M seen present in blood vessels.…”

Acute Disseminated Panniculitis Associated with Alpha-1 Antitrypsin Deficiency

“…Hemorrhage at the lesions' periphery is common, but blood vessels do not reveal primary disease or vasculitis. These findings prompt further work-up to investigate the underlying cause of panniculitis [ 3 ]. AATD should always be considered in any biopsy revealing lobular neutrophilic or necrotizing panniculitis [ 14 ].…”

“…As AAT inhibits neutrophil proteases during acute-phase response, its severe deficiency predisposes to early-onset pulmonary emphysema, primarily in smokers, and less frequently systemic vasculitis and neutrophilic panniculitis [ 3 ]. AAT trapped in the liver due to point mutations can induce organ disease through toxic “gain of function” and its persistence as endoplasmic reticulum inclusions within hepatocytes can lead to fibrosis, cirrhosis, and cancer [ 4 ].…”

Interstitial dermal infiltrate: an intriguing pattern

“…Patients suffer from lung disease (emphysema, dispone, infections), Liver involvement (Cirrhosis, hepatitis, cholestasis, hepatocellular carcinoma) and skin manifestations in the form of a Neutrophilrich infiltrates. While the condition is known to cause nodular inflammation of the subcutis in the form of a lobular or septal neutrophilic panniculitis, 33 it is important to emphasize that dermal involvement is also distinctive. Histopathology shows sheets of neutrophils separating collagen bundles in the dermis in a bottom-heavy distribution (Figure 3C and D).…”