The Sjögren-Larsson Syndrome (SSL) is a rare autoimmune disease that causes glandular inflammation, normally in salivary and lacrimal glands. It can be classified as primary, when it is isolated, or secondary, when it is concomitant with other syndromes. Several studies correlate immune diseases with bone-marrow neoplasias, between them, the Myelodysplastic neoplasms (MDS). MDS is a heterogeneous group of hematologic diseases characterized by cytopenias in one or more hematologic lineages. Also, immunological disorders and chronic immunological stimulation are shown to be a trigger to ineffective hematopoiesis in patients with genetic predisposition. This report aims to describe MDS diagnosis in a patient with a rare immune disease and to demonstrate the complications associated with this condition. Case report: A 76-year-old woman, diagnosed with secondary SSL and autoimmune hemolytic anemia (AHAI), mastectomized, returned to a follow-up declaring fatigue and indisposition. The hematologic perfil showed: direct coombs positive, reticulocytes 8.0%, hemoglobin 7.7 g/dL, leukocytes 1280, platelets 318,000, homogeneous nuclear ANA 1/640, hypergammaglobulinemia, anti-SSA 240.0 and Schirmer positive. She was submitted to multiple treatments with antihistamines and immunosuppressants, but had infectious complications and hospital admissions. In 2023, it was indicated a splenectomy due to refractory disease and she started to be followed up by a hematologist, who suggested treatment with rituximab (500 mg in two sections with intervals of 14 days) as an alternative to active AHAI secondary to SSL. The treatment showed a good clinical result with the hemoglobin increased to 10,6 g/dL. However, at the end of 2023, the patient was unable to undergo a new pulse therapy of mabthera due to changes in the follow-up examinations of previously treated breast adenocarcinoma. A new biopsy showed multiple adenopathy attributed to the SSL itself. In 2024, a new bone marrow aspirate was taken which showed dyserythropoiesis, dysgranulopoiesis, 2% blasts and, in the cytogenetics test, 47,XX,+14[4]/46,XX[16]. In this context, the patient was diagnosed with MDS with a low percentage of blasts (MDS-LB).

The immunological dysregulation and hyperactivation of T and B lymphocytes will destroy self-antigens present in the epithelium of the exocrine glands, characterizing SSL, and in the erythrocytes, as in AHAI, leading to the release of hemoglobin into the plasma and dysfunction in gas transport. Studies show that autoimmune manifestations can lead to secondary diseases in bone marrow and MDS is one of them. Recently, studies linked UBA1 somatic mutations as the recurrent cause of clinically complex diagnoses with overlapping hematologic features. This new disease entity is known as VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. VEXAS syndrome is frequently associated with hematological disorders, around 30-50% of these patients have concurrent MDS. Interestingly, the 14 trisomy finding has been associated with hematologic neoplasias and MDS overlap syndromes. In addition, it is crucial to confirm UBA1 mutation to VEXAS-associated diagnoses in this context of inflammatory clinical presentation. The correct diagnosis of MDS overlap syndromes is essential because their prognosis differs from isolated disorders and may require specific treatments due to unique molecular vulnerabilities.