Phototoxicity in EPP

Phototoxic reactions occur when erythropoietic protoporphyria (EPP) patients expose skin to light, specifically visible light, causing protoporphyrin IX to react immediately. EPP symptoms can be acute, or delayed (subacute), most often expressed as anaphylactoid reactions. During a reaction patients experience generalised oedema (swelling), effusion in tissues and distortion of the skin. As a result of the fear of phototoxic reactions, EPP patients are inevitably forced to deprive themselves of light and UV exposure.

Mechanism of action

While the exact mechanism behind EPP reactions is not fully understood, attempts have been made to learn more about what causes the symptoms reported by EPP patients.

Protoporphyrin IX (PPIX) is a photoreactive molecule. When exposed to certain wavelengths of light, PPIX absorbs photons and generates reactive oxygen species (ROS) which can then damage surrounding tissue. Most of the tissue damage takes place in the capillaries underneath the surface of the skin, with ROS attacking and damaging the interior surface of the capillaries. Mast cells are also attacked and degranulated, releasing inflammatory compounds which probably contribute to the swelling, redness and pain experienced by EPP patients after light exposure.

Phototoxic reactions

Phototoxic reactions are the most visible symptoms in EPP patients.
The symptoms of phototoxic reactions vary per patient per day. Most patients will report ‘intolerable pain’ or ‘intense burning’ under the skin due to the damage to the blood vessels caused by the reactive oxygen species which form following light or sun exposure. Most patients will show a generalised swelling (oedema) of the body parts exposed to light and in other cases generalised oedema of the entire body. A phototoxic reaction occurs after exposure to sources emitting visible light, especially blue light, which excites PPIX molecules.

The reaction, once started lasts for several days or weeks. The majority of patients experience their first phototoxic reaction as a young child, normally before the age of two, when they are first exposed to the sun. As children at this age cannot describe their complaints, often crying or screaming uncontrollably, and a lack of visible skin symptoms often leads to a misdiagnosis of behavioural or psychiatric disorders. The unspeakable ordeal for young patients, and their parents, is exacerbated by a severe delay in diagnosis.

The anaphylactoid phototoxic reaction is generally invisible, but can be accompanied by swelling (often around the eyes and mouth if exposed), reddening, blistering, crusting, bruising, and petechaie (small spot-like bleeds) and fissures in the skin. Eventually this leads to thickening and visible scarring of the burnt skin. Patients’ skin generally remains sensitive to any further light exposure, as well as to heat, air movement (such as fans) or any pressure for several days after a reaction.

Action Spectrum

Protoporphyrin IX, which accumulates in EPP patients’ skin, is a highly photoreactive molecule. When exposed to certain wavelengths of light, PPIX absorbs photons and generates reactive oxygen species (ROS). While PPIX is capable of absorbing light from both the invisible and visible spectrum (320-650nm), its absorption peak is within the so-called “Soret band”, visible purple and blue light from 400-410nm. As these wavelengths of light are capable of penetrating the upper layers of the skin, they are able to reach PPIX molecules within the lower layers of patients’ skin, causing phototoxic reactions.

Action Spectrum of EPP
Above – the Soret band action spectrum for erythropoietic protoporphyria (EPP)

For most patients outdoor exposure presents the highest risk of phototoxic reactions although artificial lights including room lighting, surgical lights and laptop screens have all been reported to cause phototoxicity. Sunlight need not be direct to cause phototoxicity in EPP, with reflective light off surfaces such as water or snow, or sunlight filtered through clouds capable of penetrating skin and triggering a reaction. Plain glass provides no protection, although coloured filters can provide some protection.

The length of light exposure required to provoke a phototoxic reaction in EPP varies greatly. Some patients are unable to tolerate more than a few seconds of light exposure. Patients also report a ‘priming phenomenon’, where an initial long exposure significantly lowers their light tolerance threshold for several days thereafter.

Unique to EPP patients (amongst conditions causing reactions to light) is the phenomenon of ‘prodromal’ symptoms: sensory reactions of the exposed skin which serve as a warning sign. Typically, these prodromal symptoms are described as ‘prickling’ sensations of the exposed skin: the afferent nerve stimulation of the exposed skin leads to the first symptoms forewarning patients against further exposure and second degree burns.

Last updated on May 27, 2016