Neutrophilic Dermatoses and Their Implication in Pathophysiology of Asthma and Other Respiratory Comorbidities: A Narrative Review

Author:

Salem Iman1,Kimak Mark1,Conic Rosalynn1,Bragazzi Nicola L.2ORCID,Watad Abdulla345,Adawi Mohammad6,Bridgewood Charlie5,Pacifico Alessia7,Santus Pierachille89,Rizzi Maurizio9,Petrou Stephen10,Colombo Delia11ORCID,Fiore Marco12ORCID,Pigatto Paolo D. M.1314,Damiani Giovanni112131415ORCID

Affiliation:

1. Department of Dermatology, Case Western Reserve University, Cleveland, USA

2. Department of Health Sciences (DISSAL), School of Public Health, University of Genoa, Genoa, Italy

3. Department of Medicine “B”, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel

4. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

5. Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds, UK

6. Padeh and Ziv Hospitals, Azrieli Faculty of Medicine, Bar-Ilan University, Ramat Gan, Israel

7. San Gallicano Dermatological Institute, IRCCS, Rome, Italy

8. Department of Biomedical Sciences L. Sacco, University of Milan, Milan, Italy

9. Respiratory Unit, Center for Sleep and Respiratory Disorders, “Luigi Sacco” University Hospital, Milan, Italy

10. Emergency Medicine, Good Samaritan Hospital Medical Center, New York, USA

11. Department of Pharmacology, University of Milan, Milan, Italy

12. Department of Women, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy

13. Clinical Dermatology, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy

14. Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy

15. Young Dermatologists Italian Network, Centro Studi GISED, Bergamo, Italy

Abstract

Neutrophilic dermatoses (ND) are a polymorphous group of noncontagious dermatological disorders that share the common histological feature of a sterile cutaneous infiltration of mature neutrophils. Clinical manifestations can vary from nodules, pustules, and bulla to erosions and ulcerations. The etiopathogenesis of neutrophilic dermatoses has continuously evolved. Accumulating genetic, clinical, and histological evidence point to NDs being classified in the spectrum of autoinflammatory conditions. However, unlike the monogenic autoinflammatory syndromes where a clear multiple change in the inflammasome structure/function is demonstrated, NDs display several proinflammatory abnormalities, mainly driven by IL-1, IL-17, and tumor necrosis factor-alpha (TNF-a). Additionally, because of the frequent association with extracutaneous manifestations where neutrophils seem to play a crucial role, it was plausible also to consider NDs as a cutaneous presentation of a systemic neutrophilic condition. Neutrophilic dermatoses are more frequently recognized in association with respiratory disorders than by chance alone. The combination of the two, particularly in the context of their overlapping immune responses mediated primarily by neutrophils, raises the likelihood of a common neutrophilic systemic disease or an aberrant innate immunity disorder. Associated respiratory conditions can serve as a trigger or may develop or be exacerbated secondary to the uncontrolled skin disorder. Physicians should be aware of the possible pulmonary comorbidities and apply this knowledge in the three steps of patients’ management, work-up, diagnosis, and treatment. In this review, we attempt to unravel the pathophysiological mechanisms of this association and also present some evidence for the role of targeted therapy in the treatment of both conditions.

Funder

National Institute of Health T32

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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