Effectiveness of pseudocatalase formulations in vitiligo

I read with great interest the article ‘Topical pseudocatalase mousse and narrowband UVB phototherapy is not effective for vitiligo: an open, single‐centre study’ by Patel et al.1 These authors showed that twice‐daily application of topical pseudocatalase mousse to the hands and face in patients with vitiligo, in combination with twice‐weekly suberthemogenic narrowband UVB phototherapy, over a treatment period of 24 weeks was not effective. This protocol even slightly worsened the patients' vitiligo.1 In addition, these authors mention the unsuccessful outcome of a recent multicentre, double‐blind, placebo‐controlled cross‐over trial of topical pseudocatalase cream and UVB phototherapy.1 I have also been participating in both trials and can confirm that the two formulations tested were not effective in achieving repigmentation in patients with vitiligo in our institution. However, there is compelling in vitro and in vivo evidence that patients with vitiligo generate and accumulate up to mM levels of hydrogen peroxide (H2O2) in their epidermis.2, 3 In addition, it has been demonstrated that these patients have low epidermal catalase levels, together with low thioredoxin reductase and glutathione peroxidase levels.4, 5 Hence the scientific rationale of mopping up the epidermal H2O2‐induced stress by topical substitution with a ‘pseudocatalase’ is more than understood.6 Furthermore, there is ample in vitro and in vivo evidence that the pseudocatalase (PC‐KUS) as originally formulated does indeed remove epidermal H2O2.7, 8 The successful removal of H2O2 together with the substitution of calcium chloride coincides with repigmentation in 60% of all patients, but stops disease progression in 95% of all patients treated so far. However, pseudocatalase activity is based on a subtle chemical complex which needs to be activated by light in order to perform the degradation of H2O2 to H2O and O2.2 Hence the complex will not be active without additional single electron photo‐oxidation. This single electron photo‐oxidation is derived from low‐dose narrowband UVB (0.15 J/cm2). In this context, it is noteworthy that the dose is never increased during the treatment period. Unfortunately, the two formulations tested in the above clinical trials were not the original formulation. These two pseudocatalase preparations, as well as two other independent copies available on the Internet, have been investigated in vivo and in vitro using Fourier Transform Raman spectroscopy and have been found to show no or little effect on H2O2 removal (K. U. Schallreuter, unpublished data). On the basis of these results, I would like to express my concern that the claim of pseudocatalase activity, as originally introduced by our group, does not hold for any of these formulations. The clinical results for low‐dose narrowband activated pseudocatalase (PC‐KUS) are in on more than 1000 patients, who showed excellent repigmentation of the face and all body sites, except for wrists, fingers and feet. The clinical effectiveness of pseudocatalase (PC‐KUS) has been documented recently in another placebo controlled study.8 In conclusion, for removal of epidermal H2O2 in vitiligo, activated pseudocatalase (PC‐KUS) in combination with calcium chloride in its original formulation is a useful treatment modality that should be available to all patients. However, it should also be noted that educated dermatologists are required to guide the patients' treatment in order to avoid unnecessary disappointment and complications.