Myelodysplastic syndromes and skin

Myelodysplastic syndrome" - MDS- is the name given to a group of clonal disorders of hematopoietic stem cells characterized by dysplasia of blood and bone marrow cells with hematopoietic insufficiency and increased risk of developing acute myeloid leukemia. The leading finding is usually anemia, and often bi- or pancytopenia. The bone marrow is often normo- or hypercellular, in about 10% of cases hypocellular. Diagnostically suggestive are dysplasia signs of one or more cell series. At least 10 % of the cells in a row must show clear signs of dysplasia for the diagnosis of MDS to be made.

In approximately 90% of cases, the cause cannot be determined with certainty (primary MDS). In 10% of cases (secondary MDS or also therapy-associated MDS > 80% chromosomal aberrations), previous chemotherapy and/or radiotherapy are known and probably causative.

Classification: see below. Myelodysplastic syndromes

Skin symptoms in MDS occur only sporadically. Several times described as so-called "neutrophilic dermatoses "was the concordant occurrence of:

• Granuloma faciale (Vázquez García J et al. 2001).
• Sweet syndrome.
• Pyoderma faciale (Rosacea fulminans).
• Pyoderma gangraenosum
• Acute pustulosis of the skin (Vignon-Pennamen MD et al. 2017; Fox MC et al. 2008).
• Panniculitis neutrophil: isolated reports.
• Specific skin infiltrations: Rarely, specific skin infiltrations by myelomonocytic cells occur. They are then usually to be taken as signs of progression of MDS. Clinico-morphologically, they appear as uncharacteristic reddish nodules or plaques (clinical and histological incidental findings) (Avivi I et al. 1999).
• Auto-immunologic manifestations: These include arthritides, thyroid disorders, osteochondritis, IgA vasculitides (e.g., Purpura Schönlein-Henoch) (Chen HC et al 2004), autoimmune cytopenias (Hochman MJ et al 2022).
• Unspecific symptoms: refer to dry and itchy skin and recurrent herpes simplex eruptions (Shimamoto Y et al. 1993).

In this context, it becomes clear that autoimmune diseases (or their therapy) are a risk factor for the development of myelodysplastic syndromes. Furthermore, a myelodysplastic syndrome can also be a trigger for an autoimmune disease. It is likely that myelodysplastic syndromes are closely associated with excessive inflammatory activity in the myeloid microenvironment. The consequence is myeloproliferative autoimmune phenomena (Hochman MJ et al. 2022). Autoimmune diseases per se may also promote clonal evolution and impaired bone marrow growth, favoring the development of myeloid proliferative syndromes. Finally, therapy-related myeloid neoplasms-including myelodysplastic syndromes-are also observed after treatment of autoimmune diseases with immunosuppressive therapies. VEXAS syndrome, first reported in 2020, is caused by a mutation in the UBA1 gene. The mutation has an activating effect on myeloid cells, which can lead to the development of a myeloid autoinflammatory syndrome.

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