IMPORTANCE VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently described severe adult-onset autoinflammatory disease that is associated with myeloid lineage-restricted ubiquitin-activating enzyme 1 (UBA1) somatic variations that primarily affect the skin (Sweet syndrome), cartilage, and bone marrow. Skin symptoms have been poorly described.OBJECTIVE To better describe clinical and pathological skin manifestations and their pathophysiology in VEXAS syndrome. DESIGN, SETTING, AND PARTICIPANTSThis multicenter retrospective case series study of clinical and histological features of 8 patients with VEXAS syndrome and skin involvement was conducted in France from December 2007 to March 2021, with molecular data obtained from March to April 2022. Any UBA1 variations were detected by Sanger or next-generation sequencing that was performed on bone marrow and formalin-fixed paraffin-embedded tissue sections of skin lesion biopsies.RESULTS All 8 patients were men, and the median age at symptom onset was 65.5 years (interquartile range, 54-76 years). All patients had neutrophilic dermatosis skin lesions, including tender red or violaceous papules, sometimes edematous, without fever, arthralgia, recurrence or pathergy, inflammatory edematous papules on the neck and trunk (sometimes umbilicated), and firm erythematous purpuric or pigmented infiltrated plaques and nodules. Three patients had livedo racemosa. The infiltrates were perivascular and consisted of mature neutrophils with leukocytoclasia, which were admixed with myeloperoxidase-positive CD163-positive myeloid cells with indented nuclei and lymphoid cells in all cases. A sequencing analysis of paired bone marrow samples and skin lesion biopsies identified the same loss-of-function UBA1 variation in both samples for all patients.CONCLUSIONS AND RELEVANCE This case series study describes the different clinical presentations of skin lesions found in VEXAS syndrome, which is characterized histologically by neutrophilic dermatosis. The findings suggested that the dermal infiltrates seen in VEXAS skin lesions are derived from the pathological myeloid clone. This suggests that using therapies that target the pathological clone may be effective in the long-term management of the disease.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with an aggressive clinical course. It is grouped with acute myeloid leukemia-related precursor neoplasms in the 2008 World Health Organization classification. Most patients with BPDCN have skin lesions at diagnosis and subsequent or simultaneous involvement of the bone marrow, peripheral blood, and lymph nodes. Patients usually respond to initial chemotherapy but often relapse. Stem cell transplantation may improve survival. This neoplasm is derived from precursors of plasmacytoid dendritic cells and is characterized by the coexpression of the immunophenotypic markers CD4, CD56, CD123, blood dendritic cell antigen-2, blood dendritic cell antigen-4, CD2AP, and lineage(-). Atypical immunophenotype expression may be present, making diagnosis difficult. BPDCN is often associated with a complex karyotype, frequent deletions of tumor suppressor genes, and mutations affecting either the DNA methylation or chromatin remodeling pathways. A better understanding of the etiology and pathophysiology of this neoplasm could open the way to new therapies targeting specific signaling pathways or involving epigenetics.

Short stature and gonad failure can be a side effect of total body irradiation (TBI). The purpose of the study was to evaluate the factors influencing final height and gonad function after TBI. Fifty young adults given TBI during childhood were included. Twenty-seven had been treated with growth hormone (GH). Those given single 10 Grays (Gy) or fractionated 12 Gy TBI had similar characteristics, GH peaks, final heights and gonad function. After the end of GH treatment, 11/20 patients evaluated had GH peak 410 lg/l. Final height was oÀ2 s.d. in 29 (58%). The height loss between TBI and final height (2.471.1 s.d.) was greater in those who were younger when irradiated (Po0.0001). When the GH-treated and -untreated patients were analyzed separately, this loss was correlated with the age at TBI at 4-8 years for the GHtreated and at 6-8 years for the untreated. Boys showed negative correlations between testicular volume and plasma follicle-stimulating hormone (FSH, P ¼ 0.0008) and between plasma FSH and inhibin B (P ¼ 0.005) concentrations. We concluded that the indications for GH treatment should be mainly based on the age at irradiation, taking into account the GH peak. The plasma FSH and inhibin B concentrations may predict sperm function.