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Severe skin reactions: clinical picture, epidemiology, etiology, pathogenesis, and treatment

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Abstract

Background

Severe skin reactions, mostly following medication use, are rare and can be associated with high mortality. A suitable treatment approach that is able to reduce mortality is needed.

Methods

Recent publications on this topic were reviewed and evaluated.

Results

In the case of the self-limiting diseases acute generalized exanthematous pustulosis (AGEP) and generalized bullous fixed drug eruption (GBFDE), there is no clear indication for systemic immunomodulating treatment, and supportive care remains the gold standard. The situation is less clear in the case of drug reaction with eosinophilia and systemic symptoms (DRESS); nevertheless, primarily in the case of severe organ involvement, systemic glucocorticosteroids are recommended. This is associated with complications and often also with virus reactivation, which may delay healing. The evidence on various immunomodulating therapies in Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is controversial. Recent publications favor steroid pulse treatment, the tumor necrosis factor (TNF)-α inhibitor etanercept, as well as the calcineurin inhibitor cyclosporine A, with the latter representing the most promising approach.

Conclusion

The rarity and unpredictability of the reactions make a randomized double-blind therapeutic trial extremely difficult. Using meta-analyses, it is possible to trace a trend in the use of systemic treatment options. Supportive care remains the most important treatment strategy for all clinical entities.

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Abbreviations

AGEP:

Acute generalized exanthematous pustulosis

ANA:

Antinuclear antibodies

BSA:

Body surface area

BW:

Body weight

CI:

Confidence interval

CMV:

Cytomegalovirus

DIHS:

Drug-induced hypersensitivity syndrome

DRESS:

Drug reaction with eosinophilia and systemic symptoms

EBV:

Epstein-Barr virus

EM:

Erythema multiforme

EMM:

Erythema multiforme majus

GBFDE:

Generalized bullous fixed drug eruption

HHV‑6:

Human herpesvirus 6

Ig:

Immunoglobulin

IL:

Interleukin

IVIG:

Intravenous immunoglobulins

NSAID:

Non-steroidal anti-inflammatory drugs

OR:

Odds ratio

PCR:

Polymerase chain reaction

SCORTEN:

Severity-of-illness score for TEN

SJS:

Stevens-Johnson syndrome

SSSS:

Staphylococcal scalded skin syndrome

Teffs:

Effector T cells

TEN:

Toxic epidermal necrolysis

Th:

T helper cells

TNF:

Tumor necrosis factor

Treg:

Regulatory T cell

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  1. Dokumentationszentrum schwerer Hautreaktionen (dZh), Department of Dermatology, Medical Center and Medical Faculty, University of Freiburg, Hauptstr. 7, 79104, Freiburg, Germany

    Maren Paulmann &  Maja Mockenhaupt

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  1. Maren Paulmann
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  2. Maja Mockenhaupt
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Correspondence to Maja Mockenhaupt.

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M. Paulmann and M. Mockenhaupt declare that they have no competing interests.

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Paulmann, M., Mockenhaupt, M. Severe skin reactions: clinical picture, epidemiology, etiology, pathogenesis, and treatment. Allergo J Int 28, 311–326 (2019). https://doi.org/10.1007/s40629-019-00111-8

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