DADA2 (deficiency of adenosine deaminase type 2) is an autoinflammatory autosomal recessive disease resulting from biallelic loss of function mutations in ADA2 gene. Initially recognized as a syndrome that manifests with fevers, polyarteritis nodosa, livedo racemosa, early-onset stroke, and mild immunodeficiency 12. The clinical phenotype has expanded significantly since the first description of this syndrome in 2014. The estimated prevalence of DADA2 could be as high as 4:100,000 3. Clinical presentation and age of onset vary widely even among related patients 123. Here, we report a case of young male with adult onset DADA2, who presented with fever, lower limbs skin rash, joint pain, and anemia resembling systemic lupus erythematous (SLE).

A 24-year-old male from consanguineous parents, presented with a 1-year history of Raynaud’s phenomenon, repeated epiodes of unexplained fever, arthralgia, morning stiffness of his hands and bilateral lower limb skin rash. He also suffered from dizziness, headache, palpitation, and exertional shortness of breath, and he was found to have anemia of hemoglobin 5.4 mg/dl. He was requiring blood transfusion every two weeks for almost a year. He never had repeated infections apart of herpes zoster twice. He had one sister who was diagnosed with Behcet’s disease in outside facility, she suffered from recurrent mouth ulcers and long standing anemia. Unfortunately, she died at age 27 from ruptured appendix. Upon physical examination of our patient, he looked pale. He had hepatosplenomegaly and palpale axillary lymph nodes. Muskuolskeltal examination did not show any evidence of arthritis. He had maculopapular rash involving his lower limbs bilaterally extending up to his thighs along with hyperpigmentation in his ankle regions Figure 1 A, C. Laboratory workup revealed microcytic hypochromic anemia of hemglobin 5.9 mg/dl without evidence of hemolysis. His Inflammatory markers ESR and CRP were remarkably elevated > 145mm/h and 6.6 mg/dl respectively. His autoimmune workup showed initially negative antinuclear antibodies (ANA) that converted to positive 1:1280, anti-double stranded DNA (anti- dsDNA) was positive 186 IU/ml, rheumatoid factor was positive 53. While antineutrophil cytoplasmic antibodies (ANCA) and lupus anticoagulant were negative. Serum amyloid was elevated 103 (normal range is <= 6.4 mg/dl). CT scan of chest, abdomen and pelvis showed few cervical, axillary, and paratracheal lymphadenopathy with significant hepatosplenomegaly. The patient underwent bone marrow aspiration and biopsy to assess for hematological malignancies explaining his persistent blood-transfuison-dependent anemia which showed pure red cell aplasia. Axillary lymph node biopsy was performed and did not show evidence of lymphoma. Skin biopsy of the maculopapular rash showed perivascular infiltration by neutrophils admixed with eosinophils in the upper dermis, and infiltration of vessel wall by these cells and extravasated red blood cells, these findings were compatible with vasculitis. Although our patient fitted the 2019 European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) for SLE, we proceeded for genetic testing given the family history of behcet’s disease and early death, and presence of pure red cell aplasia that is not explainable by lupus. Genetic testing identified two pathogenic variants, c.882-2A>G (Splice acceptor (homozygous) in ADA2. His genetic testing and clinical phenotype confirmed the diagnosis of DADA2. Tumor necrosis factor inhibitors are the mainstay treatment for patients with DADA2 2. Thus, we commenced our patient on adalimumab 40 mg subcutaneous every two weeks. Three months later, his autoinflammatory/vasculitis symptoms; fever, arthralgia, maculopapular rash, and Raynaud’s phenomenon Figure 1 A,B disappeared and his inflammatory markers significantly decreased along with his serum amyloid. Surprisingly, his anti-dsDNA did not improve and continued to increase of 755 IU/ml, anti-TNF therapy. Unfortunately, his anemia also persisted, hemglobin around 5 mg/dl, and he continued to receive blood transfusion every 2 weeks complicated with iron overload. Therefore, he was referred to a bone marrow transplant center for inborn error of immunity and underwent a successful donor-matched haematopoietic stem cell transplantation (HSCT).