Refractory Evans syndrome in two patients with spondyloenchondrodysplasia with immune dysregulation (SPENCDI) treated successfully with JAK1/JAK2 inhibition

Yael Gernez^1* Mansi Narula² Juanita Valdes Camacho³ Alma-Martina Cepika² Elizabeth G. Hoyte¹ Kirsten Mouradian² Bertil Glader² Deepika Singh⁴ Bindu Sathi⁵ Latha Rao⁵ Ana L. Tolin⁶ Kenneth Weinberg² David B. Lewis¹ Rosa Bacchetta² Katja G. Weinacht^2*

• ¹Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, School of Medicine, Stanford University, United States
• ²Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, School of Medicine, Stanford University, United States
• ³Louisiana State University Health Shreveport, United States
• ⁴Division of Rheumatology, Department of Pediatrics, Valley Children Hospital, Madera, CA, USA, United States
• ⁵Division of Hematology, Department of Pediatrics, Valley Children Hospital, Madera, CA, USA, United States
• ⁶Hospital Pediátrico Dr. Humberto Notti, Argentina

Biallelic mutations in the ACP5 gene cause spondyloenchondrodysplasia with immune dysregulation (SPENCDI). SPENCDI is characterized by the phenotypic triad of skeletal dysplasia, innate and adaptive immune dysfunction, and variable neurologic findings ranging from asymptomatic brain calcifications to severe developmental delay with spasticity. Immune dysregulation in SPENCDI is often refractory to standard immunosuppressive treatments. Here, we present the cases of two patients with SPENCDI and recalcitrant autoimmune cytopenias who demonstrated a favorable clinical response to targeted JAK inhibition over a period of more than 3 years. One of the patients exhibited steadily rising IgG levels and a bone marrow biopsy revealed smoldering multiple myeloma. A review of the literature uncovered that approximately half of the SPENCDI patients reported to date exhibited increased IgG levels. Screening for multiple myeloma in SPENCDI patients with rising IgG levels should therefore be considered.