ABSTRACT
Recent updates in the diagnosis and management of chronic inflammatory conditions can be brought together to better understand autoimmune diseases (ADs). With organ-specific or organ-limited and systemic ADs, physicians often are faced with a dilemma when making a diagnosis and may feel a kind of embarrassment when a more distinct nosological entity cannot be found. ADs often overlap with other diseases and good diagnostic procedures for ADs only become evidence-based when refined histopathologic, immunopathologic, and general laboratory analyses are available. Immunofluorescence analyses, Western blotting, CUT & RUN technology allow localization of the site of autoantibody-reactivity on the relevant DNA sequence. The Polymerase chain reaction technology and CRISPR-Cas9, the new gene editor using pools of synthetic non-coding RNAs in screening experiments, are expected to lead to advances in the diagnosis of ADs. The current use of mRNA as a vaccine against COVID-19 has increased confidence in the use of mRNA or long non-coding RNAs in the treatment strategy for ADs. The integration of new knowledge about innate immunity, the complement system, vaccinology, and senescence into the care of patients with ADs expands the therapeutic arsenal of disease-modifying drugs and allows for the repurposing of anti-cytokine monoclonal/biosimilar antibodies, originally designed for chronic inflammatory diseases, for ADs. This review article brings together some of the most relevant ideas; a case report included in this review highlights the difficulty of distinguishing between ADs, chronic inflammation, and/or granular disease.
ABSTRACT
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.