Polycythemia vera is a chronic myeloproliferative neoplasm in which the bone marrow produces too many red blood cells, driven in the vast majority of cases by the acquired JAK2 V617F mutation that keeps the JAK-STAT signaling pathway permanently switched on. Patients face elevated risks of thrombosis and, in high-risk disease, progression toward myelofibrosis or acute leukemia. Standard management has long relied on phlebotomy and cytoreductive agents such as hydroxyurea to keep blood counts down. Ruxolitinib, by contrast, is an oral targeted inhibitor of the Janus kinases JAK1 and JAK2, and it does double duty: it reduces the abnormal cell production driven by mutant JAK2 signaling while also damping down the inflammatory cytokine storm that these disorders generate, including pro-inflammatory mediators such as interleukin-6 and tumor necrosis factor. It is precisely this dual identity, cytoreductive and immunosuppressive at once, that made it the logical therapeutic experiment in this case.

The patient’s clinical course began conventionally enough. He was diagnosed with high-risk polycythemia vera and achieved hematologic complete remission on hydroxyurea, meaning his blood counts returned to and remained within normal ranges. More than five years later, however, he developed histiocytoid Sweet syndrome, an uncommon variant of a condition first described in 1964 by Robert Sweet as acute febrile neutrophilic dermatosis. Classic Sweet syndrome presents with fever, raised painful plaques and nodules, and skin biopsies showing dense infiltrates of mature neutrophils without evidence of infection. In the histiocytoid variant, the infiltrating cells are immature myeloid cells that resemble histiocytes under the microscope, expressing myeloperoxidase and often posing a genuine diagnostic challenge because they can mimic leukemia cutis, the skin infiltration of leukemic cells. Distinguishing the two matters enormously, because one is an inflammatory paraneoplastic phenomenon and the other signals overt malignant spread.

Sweet syndrome is classified into three broad categories: idiopathic or classic, drug-induced, and malignancy-associated. The malignancy-associated form most often accompanies hematologic cancers, including acute myeloid leukemia, myelodysplastic syndromes and the myeloproliferative neoplasms to which polycythemia vera belongs. The prevailing hypothesis is that the underlying clonal disorder somehow triggers a reactive, systemic inflammatory process in the skin, possibly through aberrant cytokine production by the abnormal hematopoietic cells themselves. This framing has a direct therapeutic consequence: in secondary or reactive Sweet syndrome, treating the underlying disease is considered a mainstay of therapy, not merely an adjunct. Yet the Swiss case pushes that principle into uncomfortable territory, because the underlying disease was, by every standard hematologic measure, already controlled.

Initial treatment of the skin eruption followed established practice. Corticosteroids produced a temporary complete resolution of the Sweet syndrome, which is the expected first-line response, since systemic steroids remain the most reliably effective therapy for this condition. The trouble came with tapering. At the first relapse, the eruption returned promptly whenever the prednisone dose was reduced below 10 milligrams daily, a pattern familiar to any clinician who has managed steroid-dependent inflammatory disease and a recipe for long-term steroid toxicity, including osteoporosis, diabetes, infection risk and adrenal suppression. The team then tried steroid-sparing alternatives. Both colchicine, a microtubule-disrupting agent widely used in neutrophilic dermatoses and autoinflammatory syndromes, and dapsone, an antibiotic with potent anti-neutrophilic properties, failed. The malignancy-associated histiocytoid Sweet syndrome proved refractory to both agents, leaving the patient dependent on corticosteroids with no conventional exit strategy.

At this point the treatment team made a decision grounded in pharmacological reasoning rather than precedent. Given ruxolitinib’s potent anti-inflammatory and immunosuppressive properties, and its established role in the treatment of polycythemia vera itself, they switched the patient’s cytoreductive therapy from hydroxyurea to ruxolitinib, aiming to treat both conditions with a single drug. The rationale rests on the biology of the JAK-STAT pathway. JAK1 and JAK2 transduce signals from a range of cytokine and growth factor receptors, and ruxolitinib’s inhibition of this axis suppresses not only the neoplastic clone in myeloproliferative neoplasms but also the downstream inflammatory signaling that is thought to drive paraneoplastic phenomena. In myelofibrosis, ruxolitinib is well known for reducing splenomegaly and, notably, for relieving constitutional symptoms such as night sweats and pruritus that are themselves cytokine-mediated, an effect that hinted at its broader immunomodulatory reach.

The gamble worked. Within six weeks of initiating ruxolitinib, the histiocytoid Sweet syndrome resolved completely, and the resolution proved durable: the patient maintained remission of the skin disease even after corticosteroids were discontinued entirely, while his polycythemia vera remained in hematologic remission throughout. The case therefore demonstrates two things simultaneously. First, it confirms that ruxolitinib can control steroid-refractory, steroid-sparing-agent-resistant Sweet syndrome in the setting of a myeloproliferative neoplasm. Second, and more conceptually important, it shows that clonal disease driving a paraneoplastic inflammatory syndrome can persist at a level undetectable by conventional hematologic monitoring. Hematologic complete remission, in other words, does not guarantee absence of the biological activity that fuels malignancy-associated Sweet syndrome, and the skin can serve as a sensitive readout of that residual activity.

The authors draw a practical conclusion from this that they state explicitly in their report: in patients with hematological malignancies and associated Sweet syndrome, modification of the underlying disease treatment may be considered even in the presence of hematologic complete remission, particularly when conventional Sweet syndrome therapies fail. This is a meaningful shift in emphasis. The traditional algorithm for malignancy-associated Sweet syndrome treats the skin disease and the cancer on parallel tracks, escalating skin-directed therapy with steroids, then steroid-sparing agents such as colchicine, dapsone, potassium iodide or cyclosporine, while cancer therapy proceeds independently. The Swiss case suggests that when the skin disease is refractory to that first tier, the smarter move may be to change the hematologic therapy itself, choosing an agent whose anti-inflammatory profile can reach the reactive process that conventional immunosuppressants cannot fully control.

There are, of course, the usual caveats that attach to any single-patient report. A case report establishes feasibility and biological plausibility, not efficacy; it cannot rule out spontaneous remission, and it cannot define the optimal dose, timing or patient selection for ruxolitinib in this setting. Ruxolitinib carries its own risk profile, including cytopenias and increased susceptibility to herpes zoster and other infections, which is why it is not a casual substitute for hydroxyurea in every patient. Nor is it yet clear whether the same strategy would work in Sweet syndrome associated with other hematologic malignancies, such as acute myeloid leukemia or myelodysplastic syndromes, where the cytokine milieu and clonal biology differ. What the case does establish is a testable hypothesis and a documented precedent, published with the patient’s written informed consent and conducted in accordance with the Declaration of Helsinki, that other clinicians can now build on.

Perhaps the most enduring message of the report is procedural rather than pharmacological: the authors emphasize that close collaboration between hematologists and dermatologists is essential in these cases. Histiocytoid Sweet syndrome sits precisely at the boundary between the two specialties, requiring dermatopathological expertise to distinguish it from leukemia cutis and hematological expertise to interpret what the skin eruption says about the state of the underlying clone. As targeted agents with immunomodulatory effects proliferate across oncology, the boundary cases are likely to multiply, and this Swiss patient’s six-week cure suggests that the most effective therapy for a paraneoplastic skin disease may sometimes be found not in the dermatology formulary but in the hematology one.

Subject of Research: Ruxolitinib treatment of histiocytoid Sweet syndrome associated with polycythemia vera

Article Title: Ruxolitinib-responsive histiocytoid sweet syndrome in a patient with polycythemia vera in hematologic remission – a case report

Article References: Rüfer, A., Senn, M., Kündig, T., & Zeerleder, S. (2026). Ruxolitinib-responsive histiocytoid sweet syndrome in a patient with polycythemia vera in hematologic remission – a case report. Annals of Hematology. https://doi.org/10.1007/s00277-026-07291-8

Image Credits: AI Generated

DOI: 10.1007/s00277-026-07291-8

Keywords: polycythemia vera, Sweet syndrome, histiocytoid Sweet syndrome, ruxolitinib, JAK inhibitors, hydroxyurea, corticosteroids, colchicine, dapsone, paraneoplastic dermatosis, myeloproliferative neoplasm, case report