What is the pathophysiology of polymorphous light eruption (PMLE)?

Updated: Jan 22, 2020
  • Author: Saud A Alobaida, MBBS, FRCPC; Chief Editor: Dirk M Elston, MD  more...
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The etiology of polymorphous light eruption (PMLE) is not fully known, and it is likely to be multifactorial. The appearance in families supports a genetic association. The production of neoantigens, failure to induce apoptosis, poor immune tolerance, delayed hypersensitivity reaction, and skin microbiome dysregulation are important factors in the pathogenesis of PMLE. The action spectrum is primarily UVA light, but can include UVB light. Some patients even react in the visible light spectrum. It has also been shown that UVC can cause PMLE. [3]

PMLE clusters in families, suggesting a genetic component. In a study by Millard et al, they studied 420 pair of adult twins and found that 21% of monozygotic and 18% of dizygotic twins had PMLE. [4] First-degree family history was seen in 12% compared with 4% of unaffected twins. The prevalence of PMLE in first-degree family members is seen in 20.9% of members. [5]

Actinic prurigo (AP) is thought to be a subtype of PMLE, given that they share common pathophysiology. AP tends to persist longer, and lesions can involve the mucosa, including the conjunctiva. Excoriations and scaring are other features of AP not seen in PMLE. HLA-DR4 is strongly associated with AP. [6]

Delayed hypersensitivity reaction of PMLE is supported by the study of timed biopsy samples of PMLE lesions. The CD4 subtype of T cells seen very early after exposure is replaced by CD8 lymphocytes 72 hours after irradiation. [7, 8]

Kölgen et al noted that the reduced expression of tumor necrosis factor-alpha, interleukin (IL)–4, and IL-10 in the UVB-irradiated skin of patients with PMLE. The reduction of these cytokines seems linked to a relative neutropenia and is a manifestation of decreased Langerhans cell migration and reduced TH2 skewing. [9] An impairment of these mechanisms underlying UVB-induced immunosuppression may be important in the pathogenesis of PMLE.

An increase in the IL-1 family of cytokines, in particular (IL-36 gamma), in skin lesions and peripheral blood of PMLE patients indicates an enhanced focal and systemic immune response. This further supports the enhanced immune response upon UV exposure. [10]

A study by Koulu et al assessed 48 subjects (24 patients with PMLE and 24 healthy sex-matched and age-matched controls). [11] The study found similar immunosuppression of contact sensitization to diphenylcyclopropenone due to earlier exposure to solar-simulating UV radiation between both groups. However, among patients with PMLE who were immunosuppressed by UV radiation, only one exhibited immunotolerance to the same allergen 10-24 months later (P = .023). The study concluded that impaired propensity to UV-induced, allergen-specific immunotolerance may promote recurrent PMLE.

Neutrophils may play a role in the development of PMLE. Immunohistochemical analysis by Schornagel et al in 2004 showed a significant decreased neutrophil infiltration in PMLE skin after UVB irradiation compared with healthy case control subjects (P< .05). [12] Intercellular adhesion molecule 1 (ICAM-1) and E-selectin expression on endothelial cells increased in both healthy controls and in the PMLE patients after UVB irradiation. Chemotactic response towards IL-8 and C5a was not different between PMLE patients and healthy controls. The authors concluded that PMLE is marked by an altered immune response resulting in decreased skin infiltration of neutrophils after UVB irradiation.

Apoptotic keratinocyte produce photoneoantigens and failure to clear these antigens leads to an increased immune response. In photoprovocated skin samples of PMLE patients, gene expression of apoptotic cell clearance C1S and SCARB1 are reduced. [13] This, along with the failure in immune tolerance, leads to PMLE skin lesions with light exposure. In fact, this might explain the reduced rate of skin cancer in patients with PMLE. [14, 15]

Regarding microbiome dysregulation, UV-induced changes to the skin microbiome in PMLE patients was proposed as an initiating or provoking factor in the inflammatory cascade, by antimicrobial peptide (AMP) release and activation of the innate immune system. A unique pattern of AMP was seen in PMLE patients when compared with patients with atopic dermatitis, psoriasis, or normal skin. An increase in psoriasin, RNAse7, human beta defensin-2 (HBD‐2), and LL37 are seen in PMLE, similar to psoriasis. However, PMLE patients had a lower level of HBD-3 compared with psoriasis and atopic dermatitis patients. [10, 16]

Intravascular and focal perivascular deposits of fibrin were detected in biopsy samples of PMLE papules. Vascular deposits of C3 and immunoglobulin M (IgM) were noted in a few patients. These findings may suggest that vascular injury with activation of a clotting cascade may play a role in the pathogenesis of PMLE. [17]

In some PMLE lesions induced by UVA, keratinocytes were found to express ICAM-1. [18, 19] ICAM-1 is absent from normal keratinocytes, but it is known to be strongly induced by interferon-gamma. The induction of ICAM-1 on keratinocytes results either from direct effects of UV on the promoter region of the ICAM-1 gene or from indirect effects of interferon-gamma produced by activated lymphocytes aggregating in an underlying PMLE.

The demonstration that the female hormone 17beta-estradiol prevents UV radiation–induced suppression of the contact hypersensitivity response caused by the release of immunosuppressive cytokines (IL-10) from keratinocytes might explain why the risk of PMLE is higher in females than in males and why the risk decreases in women after menopause. [20]

Some have suggested that glutathione S-transferases (GSTs) act to protect against PMLE, but a study of the isoenzymes of the GST genes GSTM1, GSTT1, and GSTP1 found no protective relationship of these isoenzymes to PMLE. [21]

It is possible that the use of tobacco makes PMLE worse. [22]

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