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Pyoderma gangrenosum: pathogenetic oriented treatment approaches

Pyoderma gangraenosum – pathogenetisch orientierte Behandlungsoptionen

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Summary

Pyoderma gangrenosum (PG) shows features of autoimmune and autoinflammatory disorders. Genetic defects which affect the inflammasome, and in particular the NLRP3 zone, can cause an abnormal secretion of interleukin 1 (IL-1). IL-1 may be involved in clinical manifestation of certain (genetic) forms of PG. IL-1 receptor antagonists reduce the activity of IL-1α and IL-1β. Mutations in the PSTPIP1 gene have been identified in patients with pyogenic arthritis, pyoderma gangrenosum and acne syndrome. In patients with a pyoderma gangrenosum, acne, and suppurative hidradenitis syndrome these mutations cannot be found and the effect of IL-1 inhibition is questionable. Another upcoming opportunity is targeted therapy by tumor necrosis factor-alfa inhibitors in steroid-resistant patients. This review has been focused on (1) the modern pathogenetic concepts, (2) the currently accepted criteria for differentiating the disease, (3) the target therapy and (4) valuable advice to the clinicians regarding a number of medicaments capable of aggravating or inducing the PG.

Zusammenfassung

Das Pyoderma gangraenosum (PG) weist Symptome der autoimmunen und autoinflammatorischen Erkrankungen auf. Genetische Defekte, die das Inflammasom beeinflussen, insbesondere die NLRP3-Zone, können zur abnormen Sekretion von Interleukin 1 (IL-1) führen. IL-1 scheint bei der klinischen Manifestation bestimmter (genetischer) Typen des PG beteiligt zu sein. IL-1-Rezeptorantagonisten reduzieren die Aktivität von IL-1α und IL-1β. Mutationen im PSTPIP1-Gen sind bei Patienten mit dem PAPA-Syndrom beobachtet worden. Bei Patienten mit einem PASH-Syndrom ließen sich derartige Mutationen nicht nachweisen. Hier ist der Einsatz von IL-1-Antagonisten fragwürdig. Eine weitere Option für steroid-resistente PG-Patienten stellt die zielgerichtete Behandlung mit Tumornekrosefaktor-a-Inhibitoren dar. In dieser Übersicht widmen wir uns folgenden Themen: 1) den modernen pathogenetischen Konzepten, 2) den aktuellen diagnostischen Kriterien, 3) der targeted therapy und 4) Hinweisen zur Induktion oder Aggravation des PG durch Medikamente.

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Abbreviations

ANA:

Antinuclear antibodies

ASC:

Apoptosis-associated speck-like protein possessing a caspase-recruiting domain (identical to TMS1)

CAMPS:

CARD 14 mediated psoriasis

CAPS:

Cryopyrin-associated periodic syndrome

CARD14:

Caspase recruitment domain-coding protein 14

CINCA:

Chronic infantile neurologic cutaneous and articular syndrome

DIRA:

Deficiency of interleukin-1 receptor antagonist

ECMPS:

Enteric-coated mycophenolate mofetil

EO-IBD:

Early-onset inflammatory bowel diseases

FACS:

Familial cold autoinflammatory syndrome

FMF:

Familial Mediterranean fever

HIDS:

Hyperimmunoglobulin D syndrome

IL:

Interleukin

IL-1Ra:

Interleukin-1 receptor antagonist

mg:

Milligram

MWS:

Muckle-Wells syndrome

NLRP3:

Nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing protein 3

NOMID:

Neonatal-onset multisystem inflammatory disease

PAPA:

Pyogenic arthritis, pyoderma gangrenosum and acne

PASH:

Pyoderma gangrenosum, acne suppurative hidradenitis

PEST:

(proline-, glutamic acid-, serine-, and threonine-rich) family of protein tyrosine phosphatases

PGA:

Pediatric granulomatous arthritis

PG:

Pyoderma gangrenosum

PRAAS:

Proteasome associated autoinflammatory syndromes

PSTIP1:

Proline-serine-threonine phosphatase-interacting protein-1

TMS1:

Target of methylation-induced silencing-1 (identical to ASC)

TNF-α:

Tumor necrosis factor alpha

TRAPS:

Tumor necrosis factor receptor associated periodic syndrome

TRECID:

Tumor necrosis factor-related chronic inflammatory diseases

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  1. Department of Dermatology and Allergology, Academic Teaching Hospital Dresden-Friedrichstadt, Friedrichstrasse 41, 01067, Dresden, Germany

    Uwe Wollina MD

  2. Policlinic for Dermatology and Venerology, University Hospital Lozenetz, Academic Educational Hospital of the Saint Kliment Ohridski University, Koiak street 1, 1407, Sofia, Bulgaria

    Georgi Tchernev MD, PhD

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  1. Uwe Wollina MD
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  2. Georgi Tchernev MD, PhD
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Correspondence to Uwe Wollina MD.

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Wollina, U., Tchernev, G. Pyoderma gangrenosum: pathogenetic oriented treatment approaches. Wien Med Wochenschr 164, 263–273 (2014). https://doi.org/10.1007/s10354-014-0285-x

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  • DOI: https://doi.org/10.1007/s10354-014-0285-x

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