Eosinophilic fasciitis may present as a paraneoplastic syndrome of hematological malignancies–A systematic review

Abstract

To the Editor: Eosinophilic fasciitis (EF) is a connective tissue disorder marked by lymphocytic and eosinophilic infiltration into skin and subcutaneous tissue.1Lebeaux D. Sène D. Eosinophilic fasciitis (Shulman disease).Best Pract Res Clin Rheumatol. 2012; 26: 449-458https://doi.org/10.1016/j.berh.2012.08.001Crossref PubMed Scopus (80) Google Scholar This leads to thickening of the fascia surrounding muscles and painful, progressive physical disability.2Onajin O. Wieland C.N. Peters M.S. Lohse C.M. Lehman J.S. Clinicopathologic and immunophenotypic features of eosinophilic fasciitis and morphea profunda: a comparative study of 27 cases.J Am Acad Dermatol. 2018; 78: 121-128https://doi.org/10.1016/j.jaad.2017.06.148Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar Reports have linked the disorder to malignancies and hematological disorders.3Haddad H. Sundaram S. Magro C. Gergis U. Eosinophilic fasciitis as a paraneoplastic syndrome, a case report and review of the literature.Hematol Oncol Stem Cell Ther. 2014; 7: 90-92https://doi.org/10.1016/j.hemonc.2013.12.003Crossref PubMed Scopus (26) Google Scholar We speculated that EF may be a paraneoplastic syndrome and conducted a systematic review to evaluate this potential relationship. We searched the PubMed and EmBase databases for “eosinophilic fasciitis” and “shulman disease” on January 16, 2022. A total of 2196 studies were screened for inclusion, yielding 489 studies with 1703 patients. Our review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines (Fig 1). Patients had a mean age of 45.4 years, with 50.4% female (n = 733/1703). The mean duration of symptoms before a diagnosis of EF was made was 11.4 months. A total of 104 malignancies were associated with EF (6.1%, n = 104/1703). Out of which 57 were non-hematological (54.5%, n = 57/104) and 47 were hematological (45.2%, n = 47/104) (Table I). Patients with EF and malignancy were older, presenting at a mean age of 58.5 years. They skewed female (54.6%, n = 37/69) and had a shorter mean duration of symptoms before diagnosis at 6.1 months.Table IMalignancies associated with eosinophilic fasciitis casesCharacteristicsDataMalignanciesn (%) Non-hematological malignancies57 (54.8)Melanoma16 (16.8)Unspecified14 (14.7)Breast9 (9.5)Lungs8 (8.4)Nonmelanoma skin cancer4 (4.2)Thyroid2 (2.1)Prostate2 (2.1)Gastrointestinal1 (1.1)Ovarian1 (1.1) Hematological malignancies47 (45.2)Plasma cell dyscrasia10 (21.1)JAK2 essential thrombocytopenia8 (17)Leukemia12 (25.5)Acute myeloid leukemia5 (10.6)Chronic myelogenous leukemia4 (8.5)Acute lymphoblastic leukemia2 (4.3)Non-Hodgkin lymphoma15 (31.9)T cell lymphoma (NOS)5 (10.6)Unspecified2 (4.3)Marginal zone lymphoma1 (2.1)Hodgkin lymphoma2 (4.3)JAK2, Janus kinase 2; NOS, not otherwise specified. Open table in a new tab JAK2, Janus kinase 2; NOS, not otherwise specified. However, 55.4% (n = 16/30) of patients with a hematological malignancy were diagnosed with EF within 6 months of the cancer diagnosis. Furthermore, 75% (n = 12/16) were diagnosed with hematological malignancy and EF concurrently. In contrast, 30.7% (n = 8/26) of patients with a nonhematological malignancy were diagnosed with EF within 6 months of the cancer diagnosis. Our review found a 6.1% malignancy rate in EF patients. Lakhanpal et al found a 10% incidence rate of hematological malignancies and EF.4Lakhanpal S. Ginsburg W.W. Michet C.J. Doyle J.A. Moore S.B. Eosinophilic fasciitis: clinical spectrum and therapeutic response in 52 cases.Semin Arthritis Rheum. 1988; 17: 221-231https://doi.org/10.1016/0049-0172(88)90008-xCrossref PubMed Scopus (0) Google Scholar Similarly, Haddad et al3Haddad H. Sundaram S. Magro C. Gergis U. Eosinophilic fasciitis as a paraneoplastic syndrome, a case report and review of the literature.Hematol Oncol Stem Cell Ther. 2014; 7: 90-92https://doi.org/10.1016/j.hemonc.2013.12.003Crossref PubMed Scopus (26) Google Scholar found hematological malignancies to occur with greater incidence than solid malignancies. The authors also found that treatment of the malignancy can eradicate symptoms of EF.3Haddad H. Sundaram S. Magro C. Gergis U. Eosinophilic fasciitis as a paraneoplastic syndrome, a case report and review of the literature.Hematol Oncol Stem Cell Ther. 2014; 7: 90-92https://doi.org/10.1016/j.hemonc.2013.12.003Crossref PubMed Scopus (26) Google Scholar Our review found that patients with malignancy were diagnosed with EF at an older age (58.5 years old). Mango et al retrospective review of 89 EF patients had a younger mean age (51.5 years old).5Mango R.L. Bugdayli K. Crowson C.S. et al.Baseline characteristics and long-term outcomes of eosinophilic fasciitis in 89 patients seen at a single center over 20 years.Int J Rheum Dis. 2020; 23: 233-239https://doi.org/10.1111/1756-185X.13770Crossref PubMed Scopus (9) Google Scholar We found that hematological malignancies often present concurrently or within 6 months of EF diagnosis. Nonhematological cancers did not present with this pattern. It is possible that EF presents as a paraneoplastic syndrome of hematological malignancy. Physicians must conduct a thorough hematological workup when presented with EF patients to rule out potential malignancy. If found, treatment of the malignancy may effectively resolve EF. Physicians must also rule out malignancy in elderly EF patients with symptomatic onset less than 6 months. The limitations of this review include missed studies and incomplete reporting of EF diagnosis and malignancies. The true frequency of EF associated with malignancy remains unclear. Future studies can discern this relationship. Research on whether successful treatment of malignancy resolves EF should also be done. Overall, our review highlights a relationship between EF and malignancy that warrants continued investigation. None disclosed.