Race for the Case answers

Diagnose this new case by Frank Z. Jing, MD, and Nessa Aghazadeh Mohandesi, MD, FAAD

A 75-year-old man with a history of gastroesophageal reflux and deep vein thrombosis presented with a six-month history of unintentional 20-pound weight loss and decreased appetite. He also reported a persistent full-body eruption for the past month, which will periodically improve without treatment but then re-intensify. The individual lesions were mildly tender to palpation. Additionally, he noted increased redness involving the ears, affecting one or both sides intermittently. He was unsure if this was related to sun exposure. He denied fevers, chills, abdominal pain, or joint pains. A recent bone marrow biopsy revealed variably cellular bone marrow with erythroid hypoplasia and no increase in blasts. His hemoglobin was 7.1 g/dL, mean corpuscular volume (MCV) 97.5 fL, platelet count 225 x 10(9)/L, leukocytes 3.0 x 10(9)/L, and erythrocyte sedimentation rate (ESR) 132 mm/h.

1. Based on the symptoms, clinical photos, and laboratory evaluation, what syndrome should you be suspicious of?

Answer: VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome. A wide range of skin presentations have been reported, including Sweet-like nodules and cartilaginous involvement with chondritis, both of which are seen in this patient. The inflammation that affected his ears spared the non-cartilaginous earlobes. Venous thromboembolism is also commonly observed which this patient previously experienced. Furthermore, the anemia, high-normal MCV, and elevated ESR should raise suspicion as well.

2. How could you confirm your suspicion in question one and what are you looking for specifically?

Answer: Perform genetic testing for a mutation in the UBA1 gene.

3. What abnormalities would you expect to see on a complete blood count?

Answer: Macrocytic anemia has been identified in 90-100% of cases. Thrombocytopenia is the next most likely finding, seen in 45-49% of cases.

4. What finding(s) would you expect to see on histopathology?

Answer: The histopathologic findings are diverse; however, neutrophilic dermatosis and leukocytoclastic vasculitis are the most frequently observed. Older, resolving lesions may reveal a lymphocytic infiltrate.

5. What is the first-line treatment for this disease?

Answer: Systemic glucocorticoids, generally at a minimum of 15-20 mg/day, are needed to control symptoms associated with VEXAS. More severe presentations may require 30-50 mg/day.