Erythropoietic protoporphyrias: Pathogenesis, diagnosis and management.

The erythropoietic protoporphyrias consist of three ultra-rare genetic disorders of the erythroid heme biosynthesis, including erythropoietic protoporphyria (EPP1), X-linked protoporphyria (XLEPP) and CLPX-protoporphyria (EPP2), which all lead to the accumulation of protoporphyrin IX (PPIX) in erythrocytes. Affected patients usually present from early childhood with episodes of severe phototoxic pain in the skin exposed to visible light. The quantification of PPIX in erythrocytes with a metal-free PPIX ≥3 times the upper limit of normal confirms the diagnosis. Protoporphyria-related complications include liver failure, gallstones, mild anaemia and vitamin D deficiency with reduced bone mineral density. The management is focused on preventing phototoxic reactions and treating the complications. Vitamin D should be supplemented, and DEXA scans in adults should be considered. In EPP1, even in cases of biochemically determined iron deficiency, supplementation of iron may stimulate PPIX production, resulting in an increase in photosensitivity and the risk of cholestatic liver disease. However, for patients with XLEPP, iron supplementation can reduce PPIX levels, phototoxicity and liver damage. Because of its rarity, there is little data on the management of EPP-related liver disease. As a first measure, any hepatotoxins should be eliminated. Depending on the severity of the liver disease, phlebotomies, exchange transfusions and ultimately liver transplantation with subsequent haematopoietic stem cell transplantation (HSCT) are therapeutic options, whereby multidisciplinary management including porphyria experts is mandatory. Afamelanotide, an alpha-melanocyte-stimulating hormone analogue, is currently the only approved specific treatment that increases pain-free sunlight exposure and quality of life.

When the diagnosis is written in the DNA: a case of erythropoietic protoporphyria in a patient with a chromosome-18 deletion.

In this case study, we describe a 21-year-old man with erythropoietic protoporphyria who sought medical attention in April 2022 for diffuse edema and erythema of the hands. These symptoms had been present since childhood and usually occurred soon after sun exposure. The patient's medical history showed that chromosome 18's long arm had partially deleted. We performed a number of tests, including measuring total erythrocyte protoporphyrin levels and utilizing a spectrofluorometer to assess the fluorometric emission peak of plasma porphyrins, based on the patient's medical history and clinical symptoms. Furthermore, a genetic analysis identified an intronic variant on one allele, c.315-48T>C (IVS3-48T>C), which is categorized as a susceptibility polymorphism, and a complete deletion of the ferrochelatase gene on the other allele. The patient's clinical condition improved following the June 2022 afamelanotide implant procedure.

Afamelanotide for Treatment of the Protoporphyrias: Impact on Quality of Life and Laboratory Parameters in a US Cohort.

BACKGROUND: Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare disorders of heme biosynthesis characterized by severe cutaneous phototoxicity. Afamelanotide, an α-melanocyte-stimulating hormone analogue, is the only approved treatment for protoporphyria and leads to increased light tolerance and improved quality of life (QoL). However, published experience with afamelanotide in the US is limited. METHODS: Here, we report on all adults who received at least one dose of afamelanotide at the Massachusetts General Hospital Porphyria Center from 2021 to 2022. Changes in the time to phototoxic symptom onset, QoL, and laboratory parameters were assessed before and during treatment with afamelanotide. RESULTS: A total of 29 patients with protoporphyria were included, 26 of whom (72.2%) received ≥2 afamelanotide implants. Among the patients who received ≥2 implants, the median time to symptom onset following sunlight exposure was 12.5 min (IQR, 5-20) prior to the initiation of afamelanotide and 120 min (IQR, 60-240) after treatment (p < 0.001). Improvements in QoL during afamelanotide treatment were measured using two QoL tools, with good correlation observed between these two instruments. Finally, we found no improvements in the median levels of metal-free erythrocyte protoporphyrin, plasma protoporphyrin, or liver biochemistries during versus prior to the initiation of afamelanotide treatment. CONCLUSIONS: This study highlights a dramatic clinical benefit of afamelanotide in relation to light tolerance and QoL in protoporphyria, albeit without improvement in protoporphyrin levels or measures of liver function.

Afamelanotide in protoporphyria and other skin diseases: a review.

Afamelanotide is a synthetic alpha melanocyte stimulating hormone presenting a higher activity than natural hormones. Its main properties are related to the enhanced production of eumelanin by agonistically binding to the melanocortin-1 receptor. Since 2016 afamelanotide has been especially applied to treat cases of erythropoietic porphyria (EPP), where painful photosensitivity has been observed since early childhood. The positive effect of afamelanotide in EPP administered subcutaneously improved tolerance to artificial white light and increased pain-free time spent in direct sunlight. In this review we summarize the possible use of afamelanotide in dermatology, with special emphasis on EPP and encourage including afamelanotide as a treatment option in patient care.

A systematic review of case series and clinical trials investigating systemic oral or injectable therapies for the treatment of vitiligo.

AIMS AND OBJECTIVES: The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions. METHOD: Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles. RESULTS: In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%). CONCLUSION: Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness.

A feasibility and safety study of afamelanotide in acute stroke patients - an open label, proof of concept, phase iia clinical trial.

BACKGROUND: Neuroprotective agents have the potential to improve the outcomes of revascularisation therapies in acute ischemic stroke patients (AIS) and in those unable to receive revascularisation. Afamelanotide, a synthetic α-melanocyte stimulating hormone analogue, is a potential novel neuroprotective agent. We set out to assess the feasibility and safety of afamelanotide for the first time in AIS patients. METHODS: AIS patients within 24 h of onset, with perfusion abnormality on imaging (Tmax) and otherwise ineligible for revascularisation therapies were enrolled. Afamelanotide 16 mg implants were administered subcutaneously on Day 0 (D0, day of recruitment), D1 and repeated on D7 and D8, if not well recovered. Treatment emergent adverse events (TEAEs) and neurological assessments were recorded regularly up to D42. Magnetic resonance imaging (MRI) with FLAIR sequences were also performed on D3 and D9. RESULTS: Six patients (5 women, median age 81, median NIHSS 6) were recruited. Two patients received 4 doses and four patients received 2. One patient (who received 2 doses), suffered a fatal recurrent stroke on D9 due to a known complete acute internal carotid artery occlusion, assessed as unrelated to the study drug. There were no other local or major systemic TEAEs recorded. In all surviving patients, the median NIHSS improved from 6 to 2 on D7. The median Tmax volume on D0 was 23 mL which was reduced to a FLAIR volume of 10 mL on D3 and 4 mL on D9. CONCLUSIONS: Afamelanotide was well tolerated and safe in our small sample of AIS patients. It also appears to be associated with good recovery and radiological improvement of salvageable tissue which needs to be tested in randomized studies. GOV IDENTIFIER: NCT04962503, First posted 15/07/2021.

Afamelanotide Is Associated with Dose-Dependent Protective Effect from Liver Damage Related to Erythropoietic Protoporphyria.

In animal models, melanocyte-stimulating hormones (MSHs) protect the liver from various injuries. Erythropoietic protoporphyria (EPP), a metabolic disorder, leads to the accumulation of protoporphyrin (PPIX). In addition to the most prominent symptom of incapacitating phototoxic skin reactions, 20% of EPP patients exhibit disturbed liver functioning and 4% experience terminal liver failure caused by the hepatobiliary elimination of excess PPIX. Skin symptoms are mitigated through the application of the controlled-release implant afamelanotide, an α-MSH analog, every sixty days. Recently, we showed that liver function tests (LFTs) improved during afamelanotide treatment when compared to before treatment. The present study investigated whether this effect is dose-dependent, as the evidence of dose dependency would support a beneficial influence of afamelanotide. METHODS: In this retrospective observational study, we included 2933 liver-function tests, 1186 PPIX concentrations and 1659 afamelanotide implant applications in 70 EPP patients. We investigated whether the number of days since the preceding afamelanotide dose or the number of doses during the preceding 365 days had an effect on LFTs and PPIX levels. In addition, we assessed the effect of global radiation. RESULTS: Inter-patient differences exerted the most prominent effect on PPIX and LFTs. In addition, PPIX increased significantly with an increase in the number of days since the last afamelanotide implant (p < 0.0001). ALAT and bilirubin decreased significantly with an increasing number of afamelanotide doses in the preceding 365 days (p = 0.012, p = 0.0299, respectively). Global radiation only influenced PPIX (p = 0.0113). CONCLUSIONS: These findings suggest that afamelanotide ameliorates both PPIX concentrations and LFTs in EPP in a dose-dependent manner.

Computational Screening of Approved Drugs for Inhibition of the Antibiotic Resistance Gene mecA in Methicillin-Resistant Staphylococcus aureus (MRSA) Strains.

Antibiotic resistance is a critical problem that results in a high morbidity and mortality rate. The process of discovering new chemotherapy and antibiotics is challenging, expensive, and time-consuming, with only a few getting approved for clinical use. Therefore, screening already-approved drugs to combat pathogens such as bacteria that cause serious infections in humans and animals is highly encouraged. In this work, we aim to identify approved antibiotics that can inhibit the mecA antibiotic resistance gene found in methicillin-resistant Staphylococcus aureus (MRSA) strains. The MecA protein sequence was utilized to perform a BLAST search against a drug database containing 4302 approved drugs. The results revealed that 50 medications, including known antibiotics for other bacterial strains, targeted the mecA antibiotic resistance gene. In addition, a structural similarity approach was employed to identify existing antibiotics for S. aureus, followed by molecular docking. The results of the docking experiment indicated that six drugs had a high binding affinity to the mecA antibiotic resistance gene. Furthermore, using the structural similarity strategy, it was discovered that afamelanotide, an approved drug with unclear antibiotic activity, had a strong binding affinity to the MRSA-MecA protein. These findings suggest that certain already-approved drugs have potential in chemotherapy against drug-resistant pathogenic bacteria, such as MRSA.

Quality-Adjusted Life Years in Erythropoietic Protoporphyria and Other Rare Diseases: A Patient-Initiated EQ-5D Feasibility Study.

Erythropoietic protoporphyria (EPP) is an ultra-rare inborn error of metabolism characterised by painful phototoxic burn injuries after short exposure times to visible light. Patients with EPP are highly adapted to their condition which makes the quantification of their health-related quality of life (QoL) challenging. In the presented patient-initiated feasibility study, we describe a new approach to assess treatment benefits in EPP by measuring QoL with the generic EQ-5D instrument in five patients under long-term (≥two years) treatment with afamelanotide, the first approved therapy for EPP. For the study, we selected patients with EPP who in addition were affected by an involuntary treatment interruption (caused by a temporary reimbursement suspension) because we hypothesized that individuals who had previously unlearned their adaptation are better able to assess their life without treatment than treatment-naïve patients. QoL under treatment was comparable to the age-matched population norm, and retrospective results for a treatment interruption and phototoxic reaction time point were comparable to the QoL of patients with chronic neuropathic pain and acute burn injuries, respectively. The results were accepted by the National Institute for Health and Care Excellence in England for their evaluation of the cost-effectiveness of afamelanotide, i.e., the calculation of quality-adjusted life years.

Vitiligo, from Pathogenesis to Therapeutic Advances: State of the Art.

Vitiligo is an acquired hypopigmentation of the skin due to a progressive selective loss of melanocytes; it has a prevalence of 1-2% and appears as rounded, well-demarcated white macules. The etiopathology of the disease has not been well defined, but multiple factors contribute to melanocyte loss: metabolic abnormalities, oxidative stress, inflammation, and autoimmunity. Therefore, a convergence theory was proposed that combines all existing theories into a comprehensive one in which several mechanisms contribute to the reduction of melanocyte viability. In addition, increasingly in-depth knowledge about the disease's pathogenetic processes has enabled the development of increasingly targeted therapeutic strategies with high efficacy and fewer side effects. The aim of this paper is, by conducting a narrative review of the literature, to analyze the pathogenesis of vitiligo and the most recent treatments available for this condition.

Immunopathogenesis and management of polymorphic light eruption.

Polymorphic light eruption (PLE) is the most common immunologically mediated photodermatosis, demonstrating many abnormalities caused by critical failure of ultraviolet (UV)-induced immunosuppression. The unique expression of antimicrobial peptides in PLE, which is most likely determined by alteration of microbiome components upon UV exposure, implicates their possible triggering role and pathogenic significance in the eruption. The review aims to clarify current knowledge regarding the immunological disturbances correlated with PLE that serve a base for better understanding of molecular pathogenesis of the disease and the development of new therapeutic strategies. Preventive treatment with broad-spectrum suncreens and sunscreens containing DNA repair enzymes, as well as natural photohardening with graduate exposure to sunlight in early spring could be sufficient in milder cases. Antioxidants and topical calcipotriol are promising approach for adjuvant prevention. Phototherapy, mainly with narrow band UVB rays, is more appropriate method in severe cases of the disease. The established treatment options for PLE include local and systemic glucocorticoids, systemic nonsedative antihistamines for itch relief, and rarely, immunosuppressive drugs in the refractory cases. Like medical photohardening, afamelanotide has the potential of photoprotection by inducing a melanization of the skin. Afamelanotide is believed to be a possible new treatment option for very severe and refractory cases of PLE. Targeting the main pruritogenic cytokine, IL-31, opens a new road for the development of novel therapeutic approaches to combat moderate and severe itching in cases of PLE with intense pruritus.

Porphyrias in the Age of Targeted Therapies.

The porphyrias are a group of eight rare genetic disorders, each caused by the deficiency of one of the enzymes in the heme biosynthetic pathway, resulting in the excess accumulation of heme precursors and porphyrins. Depending on the tissue site as well as the chemical characteristics of the accumulating substances, the clinical features of different porphyrias vary substantially. Heme precursors are neurotoxic, and their accumulation results in acute hepatic porphyria, while porphyrins are photoactive, and excess amounts cause cutaneous porphyrias, which present with photosensitivity. These disorders are clinically heterogeneous but can result in severe clinical manifestations, long-term complications and a significantly diminished quality of life. Medical management consists mostly of the avoidance of triggering factors and symptomatic treatment. With an improved understanding of the underlying pathophysiology and disease mechanisms, new treatment approaches have become available, which address the underlying defects at a molecular or cellular level, and promise significant improvement, symptom prevention and more effective treatment of acute and chronic disease manifestations.

Clinical and dermoscopic changes of acquired melanocytic nevi of patients treated with afamelanotide.

BACKGROUND: Afamelanotide (AFA) is a synthetic analogue of α-melanocyte-stimulating hormone that is approved for the treatment of patients affected by erythropoietic protoporphyria (EPP). AFA induces a "sun free" tanning and changes of acquired melanocytic nevi (AMN) that are generically described as "darkening". OBJECTIVES: To assess clinical and dermoscopic AMN changes during AFA treatment. METHODS: Adult EPP patients treated with two AFA implants 50 days apart were enrolled. They underwent a clinical and dermoscopic examination of all AMN at baseline (T0), and after 5 (T1) and 12 (T2) months from the first AFA implant. The general pattern, symmetry, number, and size of pigmented globules, morphology of the pigment network, and dermoscopic melanoma features were assessed. RESULTS: Fifteen patients were enrolled with 103 AMN. At T1 all reticular and 2-component AMN showed a focal network thickening that returned to baseline by T2. The increase of globules' number was observed at T1 but not at T2. The difference in number was not influenced by patients' age or phototype. Dermoscopic changes suggestive of malignancy were never seen. The development of new AMN was never registered. CONCLUSIONS: AFA treatment induces reversible changes of AMN dermoscopic morphology without findings suggestive of malignant transformation and it does not stimulate the development of new AMN.

Afamelanotide for prevention of phototoxicity in erythropoietic protoporphyria.

Introduction: In erythropoietic protoporphyria (EPP), an inherited disorder of heme biosynthesis, accumulation of protoporphyrin IX results in acute phototoxicity. EPP patients experience severe burning pain after light exposure, which results in a markedly reduced quality of life. Afamelanotide is the first effective approved medical treatment for EPP, acting on melanocortin-1 receptors. This article aims to review afamelanotide.Areas covered: This review summarizes the chemical properties, pharmacokinetics, safety, preclinical and clinical data on afamelanotide in EPP, and post-marketing surveillance. PubMed search, manufacturers' websites, and relevant articles used for approval by authorities were used for the literature search.Expert opinion: Afamelanotide is an α-melanocyte-stimulating hormone analog. It can activate eumelanogenesis without exposure to UV radiation. Clinical studies in EPP showed that afamelanotide treatment significantly increased exposure to sunlight and QoL. In our clinical experience afamelanotide treatment is much more effective in clinical practice than demonstrated in clinical trials and should be made available for all EPP patients meeting inclusion criteria. The 60-day interval period was not based on effectiveness studies, and therefore for some of the patients the maximum of four implants per year with the 60-day interval is insufficient. Afamelanotide is well tolerated; common adverse events were headache, fatigue, and nausea.

Beyond pigmentation: signs of liver protection during afamelanotide treatment in Swiss patients with erythropoietic protoporphyria, an observational study.

Erythropoietic protoporphyria (EPP) is an ultra-rare inherited disorder with overproduction of protoporphyrin in maturating erythroblasts. This excess protoporphyrin leads to incapacitating phototoxic burns in sunlight exposed skin. Its biliary elimination causes cholestatic liver injury in 20% and terminal liver failure in 4% of EPP patients. Thereby, the risk of liver injury increases with increasing erythrocyte protoporphyrin concentrations. Afamelanotide, an α-melanocyte-stimulating hormone (MSH) analog inducing skin pigmentation, was shown to improve sunlight tolerance in EPP. Beyond this well-known effect on pigmentation, the MSHs have liver-protective effects and improve survival of maturating erythroblasts, effects described in animal or in vitro models to date only. We investigated whether afamelanotide treatment in EPP has effects on erythropoiesis, protoporphyrin concentrations, and liver injury by analyzing retrospectively our long-term safety data. Methods: From the 47 Swiss EPP-patients treated at our center since 2006, we included those 38 patients in the current analysis who received at least one afamelanotide dose between 2016 and 2018 and underwent regular laboratory testing before and during the treatment. We compared the means of pretreatment measurements with those during the treatment. Results: Protoporphyrin concentrations dropped from 21.39 ± 11.12 (mean ± SD) before afamelanotide to 16.83 ± 8.24 µmol/L (p < .0001) during treatment. Aspartate aminotransferase decreased from 26.67 ± 13.16 to 22.9 ± 7.76 IU/L (p = .0146). For both entities, patients with higher values showed a more progressive decrease, indicating a risk reduction of EPP-related liver disease. The pre-existing hypochromia and broad mean red-cell distribution width were further augmented under afamelanotide. This was more likely due to an influence of afamelanotide on maturating erythroblasts than due to an exacerbated iron deficiency, as mean zinc-protoporphyrin decreased significantly and ferritin remained unchanged. No serious afamelanotide-related adverse events were observed for a total of 240 treatment years. Conclusion: Our findings point to a protective effect of afamelanotide on erythroblast maturation and protoporphyrin-induced liver injury. Plain Language summary: Afamelanotide, a skin tanning hormone, may protect patients with erythropoietic protoporphyria not only from skin burns, but also from liver injury associated with the disease. Patients with erythropoietic protoporphyria (EPP), an inherited metabolic disease, suffer from light-induced skin burns and liver injury elicited by the accumulated light sensitizer protoporphyrin. The excess protoporphyrin is produced in red cell precursors in the bone marrow, and it is eliminated from the body via the liver and bile. A high protoporphyrin excretion burden damages the liver cells, the risk for this increases with higher protoporphyrin concentrations. About 20% of EPP patients show some sign of liver injury and 4% develop life-threatening liver dysfunction.Afamelanotide, closely related to natural α-melanocyte stimulating hormone (MSH), induces skin tanning. This effect protects EPP patients from light-induced skin burns as shown in previous studies. We have treated Swiss EPP patients with afamelanotide since 2006, and we regularly perform safety tests of this treatment.Recent in vitro and animal studies demonstrated α-MSH effects other than skin tanning, including an improved synthesis of red blood cell precursors in the bone-marrow and protection of the liver from experimentally induced damage. Until now, it is unknown whether afamelanotide has similar effects in the human organism.To study this question, we analyzed retrospectively the safety laboratory data of 38 Swiss patients, who received at least one dose of afamelanotide from 2016 to 2019. We found that both, the average protoporphyrin concentrations and aspartate aminotransferase, a test for liver function, improved during afamelanotide treatment as compared to before.We concluded that afamelanotide applied to EPP patients to protect them from light-induced skin burns also may reduce their risk of liver injury.

[Melanocortin peptides : Fundamentals, translational research, clinical dermatology, and future perspectives]. / Melanokortinpeptide : Grundlagen, translationale Forschung, klinische Dermatologie und Zukunftsperspektiven.

Melanocortins are peptides that share a common central pharmacophor. Melanin pigmentation of interfollicular epidermis and hair via MC1R remains the key physiologic function of the naturally occurring melanocortin peptides in skin. Moreover, the melanocortins are crucially involved in the ultraviolet light-induced tanning response. Under pathophysiologic conditions, melanocortin peptides induce cutaneous hyperpigmentation, likewise via the MC1R axis, e.g. in patients with Addison's disease, ectopic precursor pro-opiomelanocortin (POMC) syndrome and in those with abnormally elevated melanocortin blood levels. Translational research on α­MSH (melanocyte-stimulating hormones) and their antagonists has further revealed a variety of other biological activities beyond pigmentation. They include cytoprotection, antioxidative effects, regulation of collagen metabolism and fibrosis, sebum production, and cutaneous wound healing. These findings have also promoted the development of novel therapies in clinical dermatology including the exploitation of afamelanotide. In 2015, this agent became the first in-class synthetic α­MSH analogue to be approved in dermatology for the treatment of erythropoetic protoporphyria. In addition to afamelanotide, setmelanotide has recently emerged as a highly selective MC4R agonist useful for the treatment of distinct forms of genetically determined obesity, e.g., POMC deficiency. Future perspectives in dermatology reside in treatment of other difficult-to-treat skin diseases with α­MSH analogues, either with topical or systemic formulations. Moreover, synthetic melanocortin peptide derivatives lacking the central pharmacophor but with maintained anti-inflammatory effects could become a promising strategy for the design of new therapies in dermatology.

Increased phototoxic burn tolerance time and quality of life in patients with erythropoietic protoporphyria treated with afamelanotide - a three years observational study.

BACKGROUND: Erythropoietic protoporphyria (EPP) is an ultra-rare genetic disorder (prevalence 1:150`000) characterized by instant painful phototoxic burn reactions in skin exposed to visible light. Afamelanotide is the first clinically tested therapy effectively increasing the time EPP patients can spend in direct sunlight without developing symptoms and reducing the number and severity of phototoxic reactions. OBJECTIVES: We report our data on real-world effectiveness of afamelanotide treatment in EPP and its phototoxic burn protection factor (PBPF). METHODS: We analysed clinical data collected between 2016 and 2018 in the Swiss EPP cohort (n = 39) on maximum phototoxic burn tolerance time (PBTT), i.e., maximum time spent in sunlight without phototoxic reaction, severity of phototoxic reactions as assessed by an 11-point Likert-type visual analogue scale (VAS), with 0 being no pain and 10 being the worst possible pain, and Quality of Life (QoL), as assessed with an EPP-specific instrument. RESULTS: Before treatment, the PBTT was median 10 min (IQR 5-20). Under treatment, PBTT increased to median 180 min (IQR 120-240). Individual PBPF increased 1.8- to 180-fold (full range, median 15). The pain severity of the worst phototoxic reaction before treatment was median 10 and under treatment median 6 (IQR 3-7). QoL at the end of the observation period in 2018 (with all the assessed patients under treatment) was 81.4% (IQR 69.4-93.4, n = 34). A 97.4% treatment adherence rate was observed. CONCLUSION: Treatment of EPP patients with afamelanotide is highly effective under real-world conditions. We suggest PBTT as a clinical meaningful endpoint in further clinical trials.

2019 FDA TIDES (Peptides and Oligonucleotides) Harvest.

2019 has been an excellent year in terms of peptides and oligonucleotides (TIDES) approved by the FDA. Despite the drop in the number of total drugs approved by the FDA in 2019 in comparison with 2018 (48 vs. 59), the total number of TIDES authorized increased (seven vs. three). Year after year, TIDES are increasingly present in therapy, as imaging agents, theragnostic and constituent moieties of other complex drugs, such as antibody drug conjugates. This means a consolidation of these kinds of drugs in the pharmaceutical arena, paving the way in the coming years for the approval of others for diverse medical indications. Here the TIDES approved in 2019 are analyzed in terms of chemical structure, medical target, mode of action, and adverse effects.

Phototherapy for Vitiligo.

Vitiligo is a common disorder with a severe impact on quality of life. The authors review recent advances in phototherapy for vitiligo focusing on narrowband ultraviolet B including mechanisms, treatment recommendations, and combination therapies. Phototherapy is the first-line treatment of choice for vitiligo with narrowband UVB preferred for widespread vitiligo and excimer used for localized lesions. However, unfamiliarity with prescribing phototherapy may be limiting clinicians from using it to its full potential. This article provides clinicians with the critical information needed to safely and effectively provide phototherapy for their patients with vitiligo.

Afamelanotide in the Treatment of Dermatologic Disease

Afamelanotide, an α-melanocyte stimulating hormone analogue, has become an emerging therapeutic option for a variety of skin conditions previously refractory to other treatments. Its efficacy has been demonstrated in several dermatologic conditions, including erythropoietic protoporphyria (EPP), solar urticaria, polymorphic light eruption (PMLE), vitiligo, acne, and Hailey-Hailey disease. Its relatively low risk side effect profile makes it an attractive treatment option and also paves the way for innovative use in other disorders.