JAK Inhibitors for Treatment of Pyoderma Gangrenosum and Sweet Syndrome: A Systematic Review of Published Case Reports

Neutrophilic dermatoses, including pyoderma gangrenosum (PG) and Sweet syndrome (SS), are inflammatory disorders characterized by neutrophilic infiltration without infection. Conventional therapies are often inadequate. We aim to evaluate the efficacy and safety of JAK inhibitors (JAK-I) in the treatment of PG and SS. The study was registered (PROSPERO-CRD420251113331), and a relevant search was conducted on PubMed/MEDLINE, Scopus, Web of Science, and Embase until July 27, 2025. Included studies were English language reports describing PG or SS treated with any JAK-I or cases of JAK-I-associated SS. Reviews, animal studies, and reports with insufficient clinical data were excluded. Four reviewers independently screened records. Data extraction included demographics, comorbidities, treatment regimens, outcomes, and adverse events. Risk of bias was assessed using the National Heart, Lung, and Blood Institute and Murad et al. tools through discussion-based consensus. Due to heterogeneous outcome definitions and small sample sizes, only descriptive synthesis was performed. Fifty-four reports, including 70 patients (59 PG, 5 SS) treated with JAK-I and 6 JAK-I-associated SS, were included. Across 43 PG studies, five JAK-Is-tofacitinib, upadacitinib, baricitinib, abrocitinib, and ruxolitinib-produced 33 complete and 26 partial responses. Twenty-six patients (44.1%) received monotherapy. Most patients (51/59; 86.4%) had at least one comorbidity. Adverse events occurred in 6 (10.1%), including anemia, hypertension, renal dysfunction, fatigue, and acneiform eruption. Among 11 SS reports, all 5 treated patients achieved complete resolution with baricitinib, ruxolitinib, or filgotinib. Six additional cases described ruxolitinib-associated SS, generally improving with corticosteroids or drug withdrawal. Most studies were rated good quality. Evidence is limited to small cases with heterogeneous outcome definitions, variable dosing, and inconsistent follow-up. JAK-Is are associated with clinical improvement in PG and selected SS cases and may serve as useful adjunct therapies, though caution is needed in patients with hematologic malignancies. Larger controlled studies are needed.