Erythema multiforme

Abstract

Erythema multiforme is an inflammatory skin and mucosal disease mainly related to infectious agents such as Herpes simplex virus, Mycoplasma pneumoniae, though it can also be "idiopathic". The characteristic skin lesions are typical or atypical acral raised target lesions. The oral mucosa can be affected, alone or in combination with other mucosal/cutaneous sites, sometimes causing extreme pain, severely impacting food intake, and warranting hospitalization. A comprehensive understanding of erythema multiforme clinical characteristics, triggering agents, and differential diagnosis including Stevens-Johnson syndrome/Toxic Epidermal Necrolysis, is crucial to conduct proper workup and management. Mycoplasma pneumoniae infection should be immediately ruled out because of the need of antibiotics. The cornerstone of management is symptomatic treatment and will be detailed in this review as well as the etiologic treatment. Lastly, the management of persistent or recurrent erythema multiforme can be challenging, especially when antivirals fail to prevent a relapse, but breakthrough treatments have been reported successful in this difficult-to-treat subset of patients.

Funding: The Funding was provided by the University of Sherbrooke Faculty of Medicine and Health Sciences.

Keywords: Erythema multiforme; Herpes simplex virus; Mycoplasma pneumoniae.

Fig. 1

Study flowchart.

Fig. 2

Acute EM: the HAEM model. The virus is phagocytosed by macrophages and CD34+ Langerhans cells progenitors which are not permissive for HSV replication resulting in viral DNA fragmentation in HSV lesions. Whereas CD34+ cells from normal subjects or from patients with HSV infection but not HAEM evidenced a time-dependent loss of viral DNA that was no longer seen at 7 days post infection, by contrast CD34+ cells from HAEM patients were impaired in viral DNA clearance, thereby providing a unique opportunity for its delivery to the skin. These viral DNA fragments are transported by the CD34+ cells to distant keratinocytes and mucosal epithelia through upregulation of adhesion molecules such as E-cadherin.^,The expression of HSV antigens results in the recruitment of CD4+ T helper type 1 cells with a subsequent release of IFN gamma and autoreactive T-cell mediated epidermal necrosis.^,

Fig. 3

Management algorithm of first EM episode. Compared to HSV-associated EM, Mycoplasma-pneumoniae induced more diffuse EM lesions, more mucositis and respiratory tract sequelae; therefore, prompt detection of MP and systematic early antibiotic treatment could improve the course of the disease. MM: mucous membrane. Systemic corticosteroids were not included in the treatment algorithm of a severe acute EM flare as their potential role will be determined by an ongoing RCT. ∗SJS: Stevens-Johnson syndrome, TEN: Toxic epidermal necrolysis.

Fig. 4

Suggested tools to measure pain and food intake in EM.