How to Treat Algodystrophy and Rheumatic Comorbidity in Myelofibrosis: Three Case Reports

Algodystrophy or complex regional pain syndrome is a chronic pain condition characterized by hyperalgesia and allodynia. Patients with algodystrophy present an amplified and persistent activation of the innate immune system, with subsequent proliferation of keratinocytes and release of proinflammatory cytokines including interleukin (IL)-6, IL-1 beta, and tumor necrosis factor-alpha (TNF-alpha). Chronic inflammation and increased levels of cytokines are observed also in Ph-negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Chronic myeloid neoplasms are characterized by overproduction of one or more mature non-lymphoid cell lineages, with erythrocytosis, thrombocytosis, and/or myeloproliferation. Three case reports described our experience in the treatment of algodystrophy and rheumatic conditions in patients with myelofibrosis; a literature search was also performed. The first patient was a 58-year-old woman who suffered from chronic myeloproliferative neoplasm in myelofibrotic evolution, under treatment with ruxolitinib and pre-treated with hydroxyurea; she reported inflammatory pain, and swelling of the tibiotarsal joints bilaterally. She was treated with neridronate 2 mg/kg for four days and methotrexate 15 mg per os per week, achieving a clinical benefit. The second patient was a 63-year-old woman diagnosed with polycythemia vera evolving to myelofibrosis. She experienced pain and swelling of the left tibiotarsal joint and difficulty walking. A therapy with low-dose steroid per os and intramuscular clodronate was administered for four months, followed by methotrexate at 15 mg per week. After two months, tenosynovitis significantly improved, as supported by the evidence of improved bone edema of the left tibiotarsal joint revealed in the magnetic resonance imaging, and pain symptoms were clinically ameliorated. The third patient was a 70-year-old male patient affected by essential thrombocythemia with myelofibrotic evolution and a paraneoplastic polymyalgia rheumatica treated with steroids and currently in remission. The patient received ruxolitinib for about two years; after the first year of treatment, he experienced pain and swelling of the right tibiotarsal joint with difficulty in walking, with a consequent diagnosis of edema and tenosynovitis, as per algodystrophy. After consulting a rheumatologist, the patient received therapy with neridronate intramuscularly with clinical benefit. As overlapping interactions and clinical manifestations between hematologic neoplasms and rheumatologic diseases exist, new clinical manifestations, such as algodystrophy, may emerge during myelofibrosis and need to be monitored in the long term by a multidisciplinary team.