Background: Sarcoidosis is a multisystem inflammatory disease characterized by the immune-mediated formation of non-necrotizing epithelioid granulomas. Several commonly used medications can induce similar granulomatous reactions, known as drug-induced sarcoid-like reactions (DISRs), which closely mimic sarcoidosis. Despite their specificity in targeting molecular pathways, certain therapies—particularly targeted treatments—have increasingly been linked to DISRs. Methods: This narrative review was based on a PubMed search using the terms “SARCOID LIKE REACTION” and “DRUG”. A cross-check was performed with “SARCOID” combined with each identified drug to identify misclassified cases. Drugs with limited evidence or weak pathogenetic plausibility were excluded, leaving only molecularly targeted therapies for consideration. Sources included case reports, case series, and reviews selected based on their clinical and scientific relevance, without any restrictions on time or language. Results: In light of the available data, five main pharmacological groups were found to be associated to DISR: immune checkpoint inhibitors, TNF-α antagonists, BRAF inhibitors, monoclonal antibodies, and miscellaneous agents. Each group has distinct mechanisms of action and clinical indications, which likely affect the frequency, presentation, and timing of DISRs. Conclusions: Diagnosing DISRs is challenging, and a structured approach is crucial for differentiating them from other conditions. To support clinicians, we propose a diagnostic algorithm to guide decision-making in suspected cases. Management should be individualized, as most DISRs either resolve spontaneously or improve after the discontinuation of the causative drug. Important factors influencing therapeutic decisions include the severity of the underlying disease, the availability of alternative treatments, and the extent of DISR manifestations.

Background: Generic formulations of pirfenidone are increasingly adopted in idiopathic pulmonary fibrosis (IPF), yet real-world evidence supporting their clinical equivalence to the originator remains limited. We aimed to evaluate whether switching from branded pirfenidone (Esbriet ^® ) to a generic formulation affects treatment efficacy or tolerability. Methods: We conducted a retrospective, within-patient observational study including consecutive patients with IPF treated with Esbriet ^® for ≥ 6 months before switching to generic pirfenidone. Pulmonary function was assessed at three time points: 6 months before the switch (T − 6), at switch (T0), and 6 months after (T + 6). The primary endpoint was the within-patient percentage change in FVC over two consecutive 6-month periods (T − 6 → T0 vs T0 → T + 6), analysed within a pre-specified equivalence framework (± 5 percentage points). Secondary endpoints included DLCO changes and treatment-related adverse events (AEs), analysed at the patient level using paired comparisons. Results: Sixty-five patients (median age 77.0 years [72.3–80.0] years, 78% male) had complete functional follow-up. The mean percentage decline in FVC was − 1.9% before the switch and − 1.7% after the switch. The estimated between-period difference in FVC change was 0.2 percentage points (95% CI − 1.1 to 1.5), fully contained within the pre-specified equivalence margins. Similar findings were observed for DLCO, with no significant difference between periods. Overall, 43% of patients experienced at least one AE during treatment. Gastrointestinal AEs were the most frequent, but paired analyses showed no significant difference in patient-level AE occurrence between branded and generic periods. No severe AEs or treatment discontinuations were observed. Conclusions: In this real-world cohort of patients with IPF, switching from branded to generic pirfenidone was not associated with clinically meaningful differences in lung function decline or treatment tolerability.

Background: The hemoglobin-to-red cell distribution width ratio (HRR) is a composite hematologic biomarker that integrates oxygen-carrying capacity and inflammation-related erythrocyte variability. Its prognostic value in idiopathic pulmonary fibrosis (IPF), and its relationship with right ventricular (RV) function, have not been established. Methods: We conducted a single-center retrospective study of 198 patients with IPF. A total of 165 patients with baseline hemoglobin, red cell distribution width (RDW) and date of diagnosis available constituted the analytical cohort. An HRR cutoff (≤0.86) was derived by time-dependent Receiver Operating Characteristic (ROC) curve analysis at 5 years. All-cause mortality from diagnosis was assessed by Kaplan–Meier and Cox regression, with bootstrap internal validation. Associations between hematologic markers and TAPSE (Tricuspid Annular Plane Systolic Excursion), PAPs (pulmonary arterial systolic pressure) and TAPSE/PASP were examined by linear and logistic regression, followed by joint stratification of HRR and RV–PA coupling. Results: Over a median follow-up of 70.3 months, 57 patients (34.5%) died. Low HRR was associated with higher mortality (72.7% vs. 15.5%; adjusted HR 3.07, 95% CI 1.68–5.63; optimism-corrected HR 2.37) and improved a clinical model beyond RDW (likelihood-ratio p = 0.012). HRR was not associated with TAPSE, PAPs, TAPSE/PASP or RV–PA uncoupling. In exploratory joint stratification, mortality rose from 11.7% with both markers preserved to 100% with both abnormal (age-adjusted HR 6.47, 95% CI 2.64–15.86). At 5 years, HRR and RDW showed similar discrimination (time-dependent AUC 0.70 and 0.71), higher than TAPSE/PASP (0.61). Conclusions: HRR is a simple, inexpensive and independent predictor of mortality in IPF that is unrelated to RV–PA coupling. The two markers provide complementary prognostic information, and their combination identifies a subgroup at very high risk. These findings require external validation.