Xeroderma Pigmentosum (XP) is a rare autosomal recessive disorder characterized by extreme ultraviolet (UV) sensitivity, predisposing patients to multiple cutaneous malignancies. We present the case of a 26-year-old male with XP diagnosed with three distinct skin cancers: Superficial Spreading Melanoma (SSM), Basal Cell Carcinoma (BCC), and Squamous Cell Carcinoma (SCC). Among these, the melanoma had metastasized. A CT scan revealed a suspicious pulmonary nodule, prompting further metabolic characterization via [18F]FDG PET/CT. The scan detected significant hypermetabolism not only in the lung lesion but also in an unsuspected right parotid gland lesion, refining disease staging and guiding treatment decisions. The patient underwent immunotherapy with nivolumab, achieving a complete metabolic response in both metastatic lesions, as confirmed by follow-up PET/CT. This case underscores the critical role of [18F]FDG PET/CT in staging and treatment monitoring for selected XP patients, a population in which advanced imaging is rarely employed. Moreover, the patient’s remarkable response to immunotherapy suggests a potential link between XP-related DNA repair defects and increased sensitivity to PD-1 blockade. These findings highlight the importance of integrating metabolic imaging into XP management and warrant further investigation into the immunogenicity of XP-associated malignancies.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by extreme ultraviolet (UV) sensitivity, predisposing patients to multiple cutaneous malignancies. We present the case of a 26-year-old male with XP diagnosed with three distinct skin cancers: superficial spreading melanoma (SSM), basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Among these, the melanoma had metastasized. A computed tomography (CT) scan revealed a suspicious pulmonary nodule, prompting further metabolic characterization via positron emission tomography/computed tomography (PET/CT) with ¹⁸F-fluorodeoxyglucose ([¹⁸F]FDG). The scan detected significant hypermetabolism not only in the lung lesion but also in an unsuspected right parotid gland lesion, refining disease staging and guiding treatment decisions. The patient underwent immunotherapy with nivolumab, achieving a complete metabolic response in both metastatic lesions, as confirmed by follow-up PET/CT. This case underscores the critical role of [¹⁸F]FDG PET/CT in staging and treatment monitoring for selected patients with XP, a population in which advanced imaging is rarely employed. Moreover, the patient’s remarkable response to immunotherapy suggests a potential link between XP-related DNA repair defects and increased sensitivity to PD-1 blockade. These findings highlight the importance of integrating metabolic imaging into XP management and warrant further investigation into the immunogenicity of XP-associated malignancies.

Photodynamic therapy (PDT) is a minimally invasive treatment choice whose clinical success in dermatology relies on the interaction between a photosensitizer, light of an appropriate wavelength, and tissue oxygen, leading to reactive oxygen species generation and selective cytotoxicity. This narrative review summarizes contemporary mechanisms and clinical evidence supporting PDT across neoplastic, inflammatory, infectious, and esthetic indications. A comprehensive literature search included randomized trials when available, systematic reviews, meta-analyses, and guideline and consensus documents, complemented by mechanistic and translational studies relevant to clinical outcomes. In premalignant and neoplastic disease, strongest evidence supports field-directed PDT for actinic keratosis and high efficacy in Bowen’s disease, with favorable cosmetic outcomes and acceptable recurrence patterns. PDT plays a more selective role in basal cell carcinoma, particularly superficial and selected nodular lesions, while its routine use as monotherapy in squamous cell carcinoma remains limited by higher recurrence. Beyond oncology, PDT shows expanding utility in acne via sebomodulatory and immunomodulatory effects, and in infectious dermatoses through broad antimicrobial activity and biofilm disruption with low resistance potential. Cosmetic applications, including photorejuvenation, benefit from protocol tailoring and combination strategies that enhance penetration and remodeling. Overall, PDT is evolving into an adaptable therapeutic framework best positioned within mechanism-oriented, multimodal algorithms.

Background/Objectives: Chronic spontaneous urticaria (CSU) is a mast-cell-driven disease with autoimmune mechanisms and an incompletely clarified aetiology, in which a substantial proportion of patients remain symptomatic despite second-generation H1-antihistamines; until recently, omalizumab was effectively the only targeted option, leaving a considerable non-responder fraction. Between February 2024 and September 2025 the landscape changed: dupilumab (anti-IL-4Rα) and the first oral Bruton tyrosine kinase (BTK) inhibitor, remibrutinib, were approved for CSU; omalizumab biosimilars reached the market; the higher-affinity anti-IgE antibody ligelizumab was discontinued; and the investigational anti-KIT antibody barzolvolimab advanced to phase 3—creating new therapeutic opportunities for non-responders while leaving the choice among these second-line options unresolved by current guidelines. We provide a critical synthesis and propose an evidence-graded process for agent selection, together with a proposed repositioning of the available agents, taking the 2022 EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline as the acknowledged reference. Methods: Critical narrative review with a structured but non-systematic search (PubMed, ClinicalTrials.gov) and a pre-specified evidence hierarchy (guideline to expert opinion); each clinical claim is annotated by its level of evidence. Results: Four agents are appraised in turn—omalizumab (anti-IgE, first-line), dupilumab (anti-IL-4Rα), remibrutinib (oral BTK inhibitor, small-molecule comparator) and barzolvolimab (anti-KIT, investigational). Current evidence appears to support omalizumab as first-line, with mechanism-guided second-line choices conditioned on endotype, comorbidity, prior biologic exposure and safety. Conclusions: The complexity of CSU and the incomplete response to currently available therapies support a patient-tailored approach to treatment selection.