Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Dermatol. Feb 2, 2018; 7(1): 1-8
Published online Feb 2, 2018. doi: 10.5314/wjd.v7.i1.1
Managing panniculitis in alpha-1 antitrypsin deficiency: Systematic review of evidence behind treatment
Donah K Sabbagh, Behrad Barmayehvar, Thanh Nguyen, Ross G Edgar, Alice M Turner
Donah K Sabbagh, the Medical Research Institute of New Zealand (MRINZ), CSB Building, Wellington Hospital, Newtown, Wellington 6021, New Zealand
Behrad Barmayehvar, Department of Colorectal Surgery, the Royal Wolverhampton Trust, Wolverhampton Road, West Midlands WV10 0QP, United Kingdom
Thanh Nguyen, Department of Intensive Care, United Lincolnshire Hospitals NHS Trust, Lincolnshire LN2 4AX, United Kingdom
Ross G Edgar, Therapy Services, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2WG, United Kingdom
Alice M Turner, Institute of Applied Health Research, University of Birmingham, Birmingham B15 2TT, United Kingdom
Author contributions: Sabbagh DK, Barmayehvar B and Nguyen T contributed equally to this work; Turner AM and Edgar RG designed the study; Edgar RG conducted the literature search; Barmayehvar B and Nguyen T screened the titles and abstracts of retrieved articles, involving a third reviewer (Edgar RG or Turner AM) where required; Turner AM and Edgar RG conducted quality assessment; Sabbagh DK extracted the data, and was checked by another (Barmayehvar B or Nguyen T); Sabbagh DK wrote the majority of the original draft of the paper in consultation with Turner AM; Barmayehvar B and Nguyen T participated in writing the paper; all authors discussed the results and commented on the manuscript; Turner AM was in charge of overall direction and planning.
Conflict-of-interest statement: Edgar RG has received non-commercial research funds from Grifols Biotherapeutics. Edgar RG reports grants from Health Education England (HEE) and the National Institute for Health Research (NIHR), outside the scope of this study.
Data sharing statement: This is not applicable to this review as only data from published works were processed and reviewed.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Dr. Alice M Turner, MBChB, MRCP, PhD, Doctor, Senior Lecturer, Honorary Consultant Respiratory Physician, Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
Telephone: +44-121-3713885 Fax: +44-121-3713887
Received: November 4, 2017
Peer-review started: November 5, 2017
First decision: November 20, 2017
Revised: November 27, 2017
Accepted: December 6, 2017
Article in press: December 6, 2017
Published online: February 2, 2018
Research background

Panniculitis is a rare manifestation of an alpha-1 antitrypsin deficiency (AATD), an already rare disease. This rarity has created a paucity in the data concerning effective management strategies of AATD-panniculitis.

Research motivation

This systematic review has investigated the available literature for the optimal management strategies for clinical resolution of AATD-panniculitis. Effective management will be helpful for both patients and clinicians, as well as opening up avenues of research allowing better understanding of this disease process.

Research objectives

To perform a systematic review of the management of patients with AATD-panniculitis, investigating interventions used and whether clinical resolution was achieved. This objective was realised, enabling the authors to advise an effective management strategy for clinical resolution. Successful management will be helpful for both patients and clinicians, as well as opening up avenues of research allowing better understanding of this disease process.

Research methods

A variety of databases were searched for appropriate papers. A title and abstract review was performed by two reviewers, and pertinent studies were obtained in full - to include 32 case reports and 4 case series. The appropriate data was extracted by one reviewer and checked by another. The nature of the data meant that only narrative synthesis was performed, and a formal assessment of quality was not applicable.

Research results

Augmentation therapy was the most successful treatment, achieving clinical resolution in 100% of managed patients. Dapsone was a cheaper alternative, achieving clinical resolution in 62%, but being very poorly tolerated. Other single-agent antibiotics were mostly unsuccessful, with the exception of doxycycline (complete resolution in 33%). Immunosuppressants were also largely unsuccessful; 80% of patients exhibited no response. Liver transplantation and therapeutic plasma exchange displayed complete resolution in 66% of patients. Other strategies, such as non-steroidal anti-inflammatory drugs (NSAIDs), or combination antibiotics, did not show sufficient response rates to recommend their use. These results contribute valuable information on effective therapeutic strategies for AATD-panniculitis. Further understanding on the mechanisms of certain therapeutic agents (e.g., dapsone/immunosuppressants) are yet to be investigated, and might unlock key concepts on the pathogenesis of panniculitis or AATD.

Research conclusions

This study suggests an effective management strategy for panniculitis presenting in AATD. Based on likelihood of complete clinical resolution and cost-implications, AATD-panniculitis should be managed with dapsone first-line, and augmentation as a second-line measure. In countries where augmentation is not available, or in cases of rapidly progressing disease, plasmapheresis may be a valuable alternative.

Research perspectives

This study has the potential to change the future management of AATD-panniculitis, both unifying an effective management strategy amongst current/future clinicians, and opening up avenues of further research to enable better understanding of this disease presentation