PRESENTATION Albert Chow, MD Pediatric Rheumatology Fellow - PowerPoint PPT Presentation

FELLOW CASE PRESENTATION Albert Chow, MD Pediatric Rheumatology Fellow 4/29/2017

Disclosures • I have no financial disclosures.

Objectives • Present a rare rheumatology case that can be seen in pediatric and adult patients • Discuss pathologic findings • Discuss potential associations between case and other rheumatologic conditions

Case – Timeline to Presentation 4/10 5/2 7/4 7/9 7/11 7/15 7/25 7/26 8/1 8/7

Case • PMHx: • Unremarkable • FHx: • SLE in a second cousin • T2DM in maternal grandma, maternal aunt, maternal uncle • Thyroid cancer in a great maternal uncle • SHx: • Is a labor worker with his step-father • Worked blueberry fields last summer • Currently working on home improvement – painting, masking, caulking, etc • Went hiking at Little Mountain in early July 2016

Initial Labs WBC 1.7 Abs Neutrophils 1139 Abs Bands 255 (15%) Abs Lymphocytes 469 Hemoglobin 11.9 Hematocrit 43.9 Platelets 75 CRP 1.9 ESR 26 D-dimer 1.9 PT / PTT / INR Normal Urinalysis Normal

Initial Exam General Ill-appearing, shaking with chills HEENT Numerous small lymph nodes along anterior and posterior cervical chains, and along clavicle CV Periods of hypotension to 90s/40s Abdomen Diffusely tender, liver and spleen edges palpated at 1 cm below costal margins Neuro Photophobia Prominent right 3 rd PIP but no joint effusions noted, mildly limited MSK ROM of fingers that may be his baseline Skin No rash or lesions

ID Consult • Recommendations: EBV IgM (-), IgG (+) CMV IgM (-), IgG (+) • EBV, CMV HIV Negative • HIV TB Negative • TB Resp viral panel Negative • Respiratory viral panel Urine GC/CT Negative • Urine GC/CT Parvo B19 Negative • Parvovirus B19 Lipase 533 • Lipase • Uric acid, LDH, ferritin • Consider abdominal imaging

Rheum / HemeOnc / GI Consults Ferritin 4280 AST 409 Triglycerides 104 ALT 452 LDH 3732 CK 118 Uric acid 2.9 Aldolase 10 439 → 177 Fibrinogen Albumin 2.8 1.9 → 2.6 D-dimer Lipase 525 Amylase 178 ANA 1:80 dsDNA 3 ANCA Negative C3 117 C4 37

Additional Studies • CT Abdomen with contrast: normal • CT Neck/Thorax with contrast: “ Mildly enlarged axillary lymph nodes bilaterally. This finding is overall nonspecific, and may be related to reactive adenopathy, a systemic inflammatory process, or underlying lymphoproliferative disease .” • Echo: normal

Pathology • Bone marrow biopsy: • “The etiology of the patient's pancytopenia is not clear. Hemophagocytosis cannot be adequately evaluated due to inadequate aspirate sample. The biopsy shows moderate increase of CD163 positive histiocytes/monocytes. There is no evidence of EBV in the marrow. Close clinical follow up is recommended. See separate report on flow (CM-16-1780 ).”

Pathology • Axillary lymph node biopsy: • “The histologic features are that of necrotizing lymphadenitis, and with the MPO positivity in the crescentic histiocytes and the CD123 plasmacytoid dendritic cells, is consistent with Kikuchi disease. There is no evidence of infection, as there are no neutrophils or granulomas. The EBER positivity is consistent with past infection. In the differential with Kikuchi disease is systemic lupus erythematosus which can have the same necrotizing lymphadenitis histology findings. Clinical correlation and follow up is recommended .”

Kikuchi Disease • Also called Kikuchi-Fujimoto Disease • Affects women more than men • Clinical features: • Fever (1 week to 1 month) • Cervical lymphadenopathy • Night sweats • Nausea / Vomiting • Weight loss • Diarrhea

Kikuchi Disease • Kucukardali et al . “Kikuchi -Fujimoto Disease: analysis of 244 cases.” Clin Rheum . 2007; 26(1):50. • Lymphadenopathy 100% • Leukopenia 43% • High ESR 40% • Fever 35% • Anemia 23% • Rash 10% • Fatigue 7% • Joint pain / Arthritis 7% • Hepatosplenomegaly 3%

Kikuchi Disease http://medpics011.blogspot.com/2014/01/kikuchi-disease.html http://www.pathpedia.com/education/eatlas/histopathology/lymph_ node/kikuchi-fujimoto_disease.aspx

Kikuchi Disease – Pathology • Histiocytic necrotizing lymphadenitis • There is presence of necrosis without neutrophils • There may be crescentic histiocytes • Immune response of T cells and histiocytes suggest an infectious trigger

Kikuchi Disease – Pathology • There is some overlap in histology of Kikuchi disease and SLE • Histiocytes stain positive for MPO • Plasmacytoid dendritic cells stain positive CD123 • But plasma cells more commonly stain positive for hematoxylin bodies in SLE

Kikuchi Disease & SLE Study Location # Cases SLE ANA Dumas et al . “Kikuchi -Fujimoto France 91 25% 45% Disease: Retrospective study of (>1:320) 91 cases and review of literature.” Medicine . 2014; 93(24): 372-82. Kucukardali et al . “Kikuchi - Turkey 244 13% 7% Fujimoto Disease: analysis of 244 cases.” Clin Rheum . 2007; 26(1):50. Kim et al . “Characteristics of Korea 140 0% 17% (1:40 – 1:80) Kikuchi-Fujimoto disease in children compared with adults.” Eur J Pediatr . 2014; 173: 111- >1:320 rare in 16. children

Case – Course & Follow-up • Hospital Day 4: Started anakinra daily • Hospital Day 10: Started prednisone • Hospital Day 13: Stopped anakinra • Hospital Day 14: Discharged home on prednisone • 2 months later (10/21/16): Tapered off prednisone