Background

1. Background 44 white male with hx of Von Willebrand’s Dz Type III, chronic Hepatitis C undergoing treatment with Interferon and Ribavirin, initially presented with 1 episode of melena. Placed on Humate-P and Amicar. EGD showed reflux esophagitis and Barrett’s esophagus. However, had recurrent fevers up to 39.7. Infectious workup including blood cultures, UA, CT sinuses, CXR unremarkable. HIV, Monospot, PPD negative. LE dopplers revealed a left sided DVT while on Humate-P and Amicar (without extension into popliteal system). Subsequent CT Chest to evaluate for PE revealed B axillary LN with largest node at 1.6 cm in R axilla. No PE present.

2. Background F/U CT Abdomen/Pelvis revealed mostly sub-centimeter, non bulky, para-aortic, aortocaval LN with largest inguinal node measuring up to 1.6 x 2.4 cm. Not amenable to excisional bx and scheduled for FNA with concern for lymphoma. FNA nondiagnostic and patient underwent BMBx with decreasing WBC. Results revealed hypercellular marrow (80%) with absence of monoclonal population. Patient also noted to have facial rash and autoimmune studies sent.

3. History HPI: Presented to UNC ED with 3 weeks h/o worsening non-productive cough, SOB, DOE (since discharge) significantly worsened over last 2 days. Increase in generalized weakness but with diminished fevers and chills over past week. Denied chest pain, pleuritic pain. Also c/o worsening rash over chest, back and arms x 7-10 days but without pruritis or tenderness. PMH: Hepatitis C (being treated with Pegasys + Ribavirin – week 28) Von Willebrand’s dz III H/O B PE in context of decompression of T-Spine from epidural hematoma 12/2003 on Humate-P

4. History Medications: Pegasys (~21 days PTA), Nexium, Levaquin (finished ~10 PTA), SH/FH: Denies tobacco use. Occ. etoh use. FH significant for Von Willebrand’s disease in both parents.

5. Physical Exam T: 39.0, P:150, RR:22, BP: 80/41, SaO2:99% RA Gen: A&O x3, Mod. Resp. distress HEENT: PERRL, Conjunctiva injected, Dry MM, sclerae anicteric, ulcerations seen on hard palate CV: Irregularly Irregular. II/VI SEM heard throughout, Pulsus: 18-20 Chest: Bibasilar crackles Abd: +BS, Soft, NT, ND Ext: No LE edema B Skin: Diffuse erythematous macular, blanching rash on chest back, arms bilaterally Neuro: CN II-XII intact. No focal deficits.

6. Labs EKG: Atrial Fibrillation with RVR at 150 bpm WBC 3.0 (ANC 1.9, ALC 0.7), Hgb/Hct: 9.3/28.9, Plts: 241,000 PT: 12.9, INR 1.0, PTT 59.2 1+ schistocytes, + spherocytes, Haptoglobin <22, LD 2451, T.B. 0.5, Reticulocyte 1.9% Na 135, K 4.8, Cl 105, HCO3 23, BUN 20, CR 1.2, Gluc 90, Albumin 2.4 CK 398, CKMB 2.9, Trop I 0.048 TSH 8.21 (3.03 on 11/24/05) UA: 2+ Protein, 3+ Blood

7. Studies CT Chest: No PE, Moderate pericardial effusion, B axillary LN with largest 1.5 cm TTE: Moderate to large circumferential pericardial effusion w/ abnormal Right ventricular diastolic filling and increased respiratory variation

8. Additional Labs: ANA >1:640 (ANA 1:40 on 8/27/03) dsDNA 1:5120 Histone Abs: 13U (0-1.5) RNP Ab +, SSA Ab +, SSB +, Jo-1 Ab +, SCL Ab -, SM Ab – Cryoglobulins + (IgG,IgM) C3: 54 mg/dL (93-222), C4: 5 mg/dL (13-52) Skin Bx: Interface dermatitis with atrophy c/w lupus or lupus like drug eruption

9. IFN-a Induced Autoimmune Disease Usman Shah

10. IFN-a Type I IFN gene cluster at chromosome 9p22 includes 13 distinct IFN-a genes as well as b, w, k, t All bind a common receptor complex (IFNAR1 and IFN AR2) and initiate JAK/STAT signaling cascade leading to transcription of target genes for host protection and viral elimination IFN also promotes survival and differentiation of mature lymphocytes, class switching, and activation of dendritic cells.

11. IFN-a Primary source of type I IFNs are natural IFN producing cells (NIPCs) or plasmacytoid dendritic cells. Viral infection generally causes significant leukocyte release of IFN-a Commonly used as treatment for Hepatitis B and C, CML, NHL, MM, Behcet’s disease, cryglobulinemia, Kaposi’s sarcoma

12. IFN-a Therapy with IFN-a has been associated with the exacerbation of pre-existing or even induction of autoimmune disease including SLE, RA, polymyositis, sarcoidosis Also known to cause pernicious anemia, thyroid disease, autoimmune hepatitis, vitiligo and DM.

13. IFN-a Induced Autoimmuninity