New Findings in PiZZ alpha1-antitrypsin deficiency-related panniculitis. Demonstration of skin polymers and high dosing requirements of intravenous augmentation therapy - PubMed (original) (raw)

Case Reports

B Gross et al. Dermatology. 2009.

Abstract

Panniculitis is a recognized but unusual complication of a severe deficiency of alpha1-antitrypsin (AAT), with fewer than 100 cases described to date. Like the pathogenesis of emphysema in severe PiZZ deficiency of AAT, panniculitis has been hypothesized to be an inflammatory process, possibly related to Z AAT polymer formation and to an unopposed anti-inflammatory screen in the context of deficient serum levels of AAT. The current report presents a 31-year-old woman with PiZZ AAT deficiency-associated panniculitis. Our case extends current knowledge of AAT-associated panniculitis in 2 ways: (1) we demonstrate Z-type AAT polymers in the skin, which supports the inflammatory pathogenesis of panniculitis and the potential pro-inflammatory role of polymers; (2) we show that a high dose and long-term use of intravenous augmentation therapy (90 mg/kg body weight once weekly during 3 years) can ameliorate the frequency and severity of panniculitis associated with AAT deficiency.

Copyright 2009 S. Karger AG, Basel.

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Figures

Fig. 1.

Fig. 1.

Proximal thigh (a) and left upper arm (b) before augmentation therapy was begun.

Fig. 2.

Fig. 2.

Acute lobular and septal panniculitis in skin punch biopsy. The arrows indicate inflammatory infiltrate and focal lobular fat cell degeneration. HE. ×40 (a), ×100 (b) and ×400 (c).

Fig. 3.

Fig. 3.

Immunostaining of skin biopsy from the reported PiZZ AAT patient (a) and from a control PiMM AAT individual (b). a Specific staining of subcutaneous fatty tissue with mouse monoclonal ATZ11 antibody (1:100) specific to polymeric form of AAT can be seen in our PiZZ patient. Original magnification ×400. The arrows indicate Z AAT polymers (brown). b No positive staining with ATZ11 antibody (1:100) can be detected in skin biopsy from the control PiMM individual. Original magnification ×100.

Fig. 4.

Fig. 4.

AAT serum levels prior to next infusion during 36 weeks of augmentation therapy administered to the patient during 2004–2005. The augmentation therapy was started on 17 April 2004 at a dose of 60 mg/kg once weekly. The dose of augmentation therapy was increased to 90 mg/kg between weeks 6 and 20 and went up to 130 mg/kg body weight between weeks 20 and 36. On this dose regimen, the patient's trough serum level of AAT rose to a maximum of 127 mg/dl. Subsequently, the dose was reduced to a maintenance regimen of 90 mg/kg body weight once weekly. No recurrence of panniculitis has been observed over augmentation therapy for a total of 3 years to date.

References

    1. Potempa J, Korzus E, Travis J. The serpin superfamily of proteinase inhibitors: structure, function, and regulation. J Biol Chem. 1994;269:15957–15960. - PubMed
    1. Hutchison DC. Natural history of alpha-1-protease inhibitor deficiency. Am J Med. 1988;84:3–12. - PubMed
    1. Janciauskiene S. Conformational properties of serine proteinase inhibitors (serpins) confer multiple pathophysiological roles. Biochim Biophys Acta. 2001;1535:221–235. - PubMed
    1. Kalsheker N, Morley S, Morgan K. Gene regulation of the serine proteinase inhibitors alpha1-antitrypsin and alpha1-antichymotrypsin. Biochem Soc Trans. 2002;30:93–98. - PubMed
    1. Carrell RW, Jeppsson JO, Laurell CB, Brennan SO, Owen MC, Vaughan L, Boswell DR. Structure and variation of human alpha 1-antitrypsin. Nature. 1982;298:329–334. - PubMed

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