Cutaneous porphyrias part II: treatment strategies

Abstract

The porphyrias are diverse in pathophysiology, clinical presentation, severity, and prognosis, presenting a diagnostic and therapeutic challenge. Although not easily curable, the dermatological manifestations of these diseases, photosensitivity and associated cutaneous pathology, can be effectively prevented and managed. Sun avoidance is essential, and patient education regarding the irreversibility of photocutaneous damage is a necessary corollary. Beyond preventative measures, the care of fragile, vulnerable skin, and pain management, each of the porphyrias has a limited number of unique additional therapeutic options. Many of the treatments have been published only in small case series or anecdotal reports and do not have well-understood nor proven mechanisms of action. This article presents a comprehensive review of available therapeutic options and long-term management recommendations for the cutaneous porphyrias.

Radiation and chemotherapy with no excessive toxicity in a patient with human papillomavirus-related tonsillar cancer and porphyria cutanea tarda: Case report and literature review

“…This occurs predominately at wavelengths 400‐410 nm (the Soret band) as well as 4 additional absorption bands of decreasing intensity in the range of 500‐700 nm. Absorption at these wavelengths cause porphyrins to produce singlet oxygen molecules that form free radicals in tissue and lead to oxidative damage . In addition, Lim proposed that photoactivation of the complement system with uroporphyrin leads to the activation of mast cells and the release of proteases.…”

“…Absorption at these wavelengths cause porphyrins to produce singlet oxygen molecules that form free radicals in tissue and lead to oxidative damage. 2 In addition, Lim 11 proposed that photoactivation of the complement system with uroporphyrin leads to the activation of mast cells and the release of proteases. These proteases cause dermal-epidermal separation.…”

“…These molecules become catalyzed and form free radicals on exposure to ultraviolet‐A, particularly in the violet spectrum (350‐400 nm). The mechanism of tissue damage is thought to be oxidative damage from free radicals that leads to skin manifestations, which can include burning sensation, vesicle formation, scarring, and, in severe cases, tissue damage with loss of digits, and facial appendages …”

Protoporphyrin IX: the Good, the Bad, and the Ugly

“…Pharmacological approaches have included pharmaceutical-grade b-carotene, narrow wave UVB phototherapy, cysteine, afamelanotide, antihistamines, and vitamin C (Table 1) (Sawyer et al, 1980;Krook and Haeger-Aronsen, 1982;Mathews-Roth et al, 1994;Collins and Ferguson, 1995;Warren and George, 1998;Wahlin et al, 2011a;Fabrikant et al, 2013;Tintle et al, 2014;Biolcati et al, 2015;Langendonk et al, 2015;Lengweiler et al, 2015;Minder and Schneider-Yin, 2015). Minder et al (2009) reviewed the treatment options for dermal photosensitivity in EPP in 2009 and concluded that the data were insufficient to prove efficacy of any treatments studied in EPP.…”

Menthol reduces phototoxicity pain in a mouse model of photodynamic therapy

“…Phototoxicity is relatively common in patients prescribed photoactive drugs and is the basis for photodynamic therapy (PDT) [19,27,28,38]. Phototoxicity also occurs in the light-exposed skin of patients suffering from erythropoietic protoporphyria (EPP) in whom the photoactive molecule protoporphyrin IX (PpIX) accumulates [18,36]. When exposed to light, fluorescent molecules generate reactive singlet oxygen ( 1 O 2 ) from triplet oxygen by a type two reaction and free radicals, such as superoxide, by a type one reaction [12].…”