Is HMME-PDT the First Choice of Treatment for Young Children With Port-Wine Stain Birthmarks?

Recently, Lasers in Surgery and Medicine published a meta-analysis based on 40 PDL studies and 18 HMME-PDT studies [1]. The authors indicate that “HMME-PDT has emerged as the first choice for PWB treatment, particularly for young children” and at the same time raise many questions regarding the use of HMME-PDT in China. On behalf of the Consensus Development Expert Group of Expert consensus on HMME-PDT, I appreciate American colleagues' interest and concern in HMME-PDT.

PDT's potential for PWS treatment was suggested in the mid-1980s and PDT protocols were developed for PWS treatment in China in the early 1990s [2, 3]. Two photosensitizing drugs, HiPorfin and Hemoporfin (also known as HMME) are approved for PWS treatment. There is no specific age restriction in HiPorfin production information. Because HMME Phase II and III trials only included patients > 14 years old, “lack of pediatric information in prescribe drug label” is stated in HMME production information. The post-marketing requirements suggest including pediatric patients in Phase IV trials to benefit them more. Clinical trials have been launched for 7−14 years old (NCT03125057, CTR20170189) and 2−7 years old (NCT04106258), respectively. Concerning “young children,” with therapeutic intention and on the premise of obtaining explicit informed consent from the parents, I believe the prescribing of HMME-PDT is regulatory adherence and in compliance with current regulations of rational off-label use of medicines [4-6].

The authors cite a paper published in 1934 and state that “hematoporphyrin derivatives have been used as antidepressants, indicating potential effects on brain function by this category of compounds. Therefore, the risk of HMME exposure to CNS in neonates, infants, and young children cannot be ignored.” In fact, the paper suggests it requires “intramuscular and oral administration of hematoporphyrin hydrochloride for an average period of 50 to 60 days” to see psychological benefit in depressive psychoses [7]. The remote risk of short-term HMME exposure to CNS in young children is likely small. Neurological and neuropsychiatric adverse reactions similar to that of porphyria have not been reported for HMME-PDT.

PDT was used before PDL became available in China. Partially due to this historical reason, many patients and parents would consider PDT as the first choice. For PDL resistance cases and large PWS lesions, clinicians might be inclined more toward PDT. But I am not aware that any publication implies “the use of HMME-PDT as the first choice of treatment for young children.” Hence, it is intriguing that the authors suggest that “HMME-PDT has emerged as the first choice for PWB in many major hospitals in China.” When accurate and thoughtfully presented, reporting of comparison of different modalities should be appreciated. In return, the authors who prefer one modality over another should have factual accuracy, giving appropriate and balanced consideration to the credible evidence supporting or opposing a particular modality. Unfortunately, a great amount article is opinion rather than factual-based. In my view, many data sets and baselines of the two groups are not fully comparable. However, this is acceptable as long as the limitations of the analysis were explained and the results were interpreted with great caution. Without a doubt, one cannot conclude whether PDT should be considered as the first choice only based on one meta-analysis.

Nevertheless, to ensure the safe, consistent, and proper use of HMME-PDT, we compiled the Expert consensus on HMME-PDT for treating port-wine stains (2024) according to the Reporting Items for Practice Guidelines in Healthcare (RIGHT), which was registered at the International Practice Guidelines Registry Platform (PREPARE-2022CN610) [8]. We look forward to engaging in insightful discussions with American colleagues on HMME-PDT.