A 78-year-old Swiss man with high-risk polycythemia vera saw his histiocytoid Sweet syndrome resolve completely within six weeks of switching from hydroxyurea to ruxolitinib — and the resolution held after corticosteroids were stopped entirely. The case, reported by Axel Rüfer, Madleina Senn, Thomas Kündig, Sacha Zeerleder and colleagues at Luzerner Kantonsspital and University Hospital Zürich, was published as an open-access article in Annals of Hematology on 30 September 2026 (DOI: 10.1007/s00277-026-07291-8).

What makes the report remarkable is timing. The patient's polycythemia vera was already in hematologic complete remission when the painful inflammatory skin eruption appeared and relapsed. By every conventional hematologic measure, the underlying malignancy was controlled. The skin said otherwise.

Polycythemia vera is a chronic myeloproliferative neoplasm in which the bone marrow overproduces red blood cells, driven in the vast majority of cases by the acquired JAK2 V617F mutation that keeps JAK-STAT signaling permanently switched on. Standard management relies on phlebotomy and cytoreductive agents such as hydroxyurea. Ruxolitinib, an oral JAK1/2 inhibitor, does double duty: it suppresses the abnormal cell production driven by mutant JAK2 while damping the inflammatory cytokine output these disorders generate, including interleukin-6 and tumor necrosis factor.

A diagnostic and therapeutic impasse

The patient's course began conventionally. Diagnosed with high-risk polycythemia vera, he achieved hematologic complete remission on hydroxyurea. More than five years later he developed histiocytoid Sweet syndrome, an uncommon variant of the condition Robert Sweet first described in 1964 as acute febrile neutrophilic dermatosis. Classic Sweet syndrome presents with fever, raised painful plaques and nodules, and biopsy shows dense infiltrates of mature neutrophils without infection. In the histiocytoid variant, the infiltrate consists of immature myeloid cells expressing myeloperoxidase that resemble histiocytes — and can closely mimic leukemia cutis.

That distinction matters enormously. One is a reactive paraneoplastic phenomenon; the other signals overt malignant spread. Sweet syndrome is classified as idiopathic/classic, drug-induced, or malignancy-associated, and the malignancy-associated form most often accompanies hematologic cancers — acute myeloid leukemia, myelodysplastic syndromes and the myeloproliferative neoplasms. The prevailing hypothesis holds that the clonal disorder triggers a reactive systemic inflammatory process, possibly through aberrant cytokine production by abnormal hematopoietic cells.

Treatment followed the established algorithm first. Systemic corticosteroids produced complete resolution — the expected first-line response. The trouble came with tapering: at first relapse, the eruption returned promptly whenever prednisone dropped below 10 mg daily, a pattern that invites long-term steroid toxicity including osteoporosis, diabetes, infection risk and adrenal suppression. Both steroid-sparing alternatives failed. Colchicine, a microtubule-disrupting agent widely used in neutrophilic dermatoses, and dapsone, with its potent anti-neutrophilic properties, left the malignancy-associated histiocytoid eruption refractory and the patient steroid-dependent with no conventional exit.

A pharmacological rationale, not precedent

The team then made a decision grounded in pharmacology rather than precedent. Given ruxolitinib's anti-inflammatory and immunomodulatory profile and its established role in 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 JAK-STAT biology: JAK1 and JAK2 transduce signals from a range of cytokine and growth factor receptors, and inhibiting the axis suppresses both the neoplastic clone and the downstream inflammatory signaling thought to drive paraneoplastic phenomena. In myelofibrosis, ruxolitinib is already known to relieve cytokine-mediated constitutional symptoms such as night sweats and pruritus — a hint of its broader immunomodulatory reach.

The gamble worked. Within six weeks of starting ruxolitinib, the histiocytoid Sweet syndrome resolved completely. The remission proved durable: the skin disease stayed controlled even after corticosteroids were discontinued entirely, while polycythemia vera remained in hematologic remission throughout.

The report demonstrates two things at once. First, ruxolitinib can control steroid-refractory Sweet syndrome resistant to steroid-sparing agents in the setting of a myeloproliferative neoplasm. Second, and conceptually more important, clonal disease driving a paraneoplastic inflammatory syndrome can persist at a level undetectable by conventional hematologic monitoring. Hematologic complete remission does not guarantee absence of the biological activity fueling malignancy-associated Sweet syndrome — and the skin can serve as a sensitive readout of that residual activity.

The authors state the practical implication explicitly: 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. That shifts the traditional algorithm, which runs the skin disease and the cancer on parallel tracks — escalating through steroids, then colchicine, dapsone, potassium iodide or cyclosporine — toward changing the hematologic therapy itself when the first tier fails.

Caveats and collaboration

The usual constraints of a single-patient report apply. A case report establishes feasibility and biological plausibility, not efficacy; it cannot exclude spontaneous remission or define optimal dose, timing and patient selection. Ruxolitinib carries its own risks, including cytopenias and increased susceptibility to herpes zoster and other infections, and it is not a casual substitute for hydroxyurea in every patient. Whether the strategy transfers to Sweet syndrome associated with acute myeloid leukemia or myelodysplastic syndromes, where cytokine milieu and clonal biology differ, remains untested. The report was published with the patient's written informed consent and conducted in accordance with the Declaration of Helsinki.

The authors' most enduring point is procedural. Close collaboration between hematologists and dermatologists is essential in these cases: histiocytoid Sweet syndrome sits precisely at the specialty boundary, requiring dermatopathological expertise to distinguish it from leukemia cutis and hematological expertise to interpret what the eruption says about the clone. As targeted agents with immunomodulatory effects proliferate across oncology, such boundary cases are likely to multiply — and this patient's six-week response suggests the most effective therapy for a paraneoplastic skin disease may sometimes sit in the hematology formulary rather than the dermatology one.