Background: Durvalumab, a PD-L1 inhibitor used as consolidation therapy after chemoradiation in unresectable stage III non–small cell lung cancer (NSCLC), can induce immune-related adverse events, among which immune-mediated pneumonitis represents one of the most severe. Differentiating checkpoint inhibitor pneumonitis (CIP) from infectious pneumonia is challenging due to overlapping clinical and radiologic findings. Case presentation: We describe a 67-year-old woman with stage III lung adenocarcinoma treated with chemotherapy, radiotherapy, and durvalumab, who presented with progressive dyspnea and extensive bilateral ground-glass opacities on CT imaging. Laboratory tests revealed leukopenia and elevated inflammatory markers. Despite broad-spectrum antibiotic and antiviral therapy, her condition worsened, requiring high-flow nasal cannula oxygen therapy. Multiplex molecular testing on sputum identified human metapneumovirus (HMPV), while blood cultures and urinary antigens for Streptococcus pneumoniae and Legionella pneumophila were negative. A pulmonology consultation raised suspicion for severe durvalumab-induced pneumonitis exacerbated by viral infection. High-dose methylprednisolone (2 mg/kg/day) followed by a four-week taper led to gradual clinical and radiologic resolution. Durvalumab was permanently discontinued. Discussion: To our knowledge, this is the first reported case of HMPV-associated pneumonitis in a patient receiving durvalumab. This case highlights the potential synergistic interplay between viral infection and immune checkpoint blockade, resulting in severe lung injury. Comprehensive microbiologic evaluation, including molecular diagnostics, is essential to guide therapy and distinguish infectious from immune-mediated causes. Conclusions: Early recognition of mixed infectious and immune-mediated pneumonitis, and timely corticosteroid therapy are critical to achieving favorable outcomes and preventing irreversible pulmonary damage.

Background: Syphilis can present with diverse clinical manifestations, earning the name “great imitator.” Malignant syphilis (MS) is a rare, severe form of secondary syphilis, typically reported in immunocompromised patients, particularly those living with HIV. However, MS can occasionally occur in immunocompetent individuals, posing diagnostic challenges due to its atypical presentation. Methods: A case report is presented alongside a PubMed literature search using the terms “(malignant syphilis OR lues maligna) AND (immunocompetent) AND (case report OR case series).” No language or temporal restrictions were applied, yielding 18 relevant publications. Results: A 60-year-old HIV-negative man presented with fever, weight loss, papular lesions, and a single ulcer on the sternum. Serology was positive for syphilis, and PCR confirmed T. pallidum DNA in the lesion. Treatment with a single intramuscular dose of benzathine penicillin G led to prompt clinical and serological improvement. Literature review (n = 18) showed that MS in immunocompetent patients affects both sexes (55% male; mean age 37.1 years), often presents with ulceronodular or rupioid crusted lesions, and frequently involves systemic symptoms. Molecular diagnostics were rarely reported, with most diagnoses relying on histopathology and serology. Treatment with benzathine penicillin G was effective in all cases, and full recovery was achieved. Conclusions: MS can occur in immunocompetent, HIV-negative individuals without obvious risk factors. Clinicians should maintain a high index of suspicion in cases of systemic, cutaneous, or ocular manifestations suggestive of MS. Molecular assays can facilitate diagnosis and prevent unnecessary invasive procedures. Benzathine penicillin G remains the treatment of choice, demonstrating high therapeutic effectiveness. MS should be considered in the differential diagnosis of ulcerative or nodular dermatoses, regardless of immune status.