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Fever, Endocarditis, and Palpable Purpura

Fever, Endocarditis, and Palpable Purpura. Neha Ohri MD, University of Colorado Hospital, Robert Janson MD,  VA Eastern Colorado Health Care System. Case. 71M presented with multiple palpable purpura on his LE to his PCP in 1/13. Nonpainful and nonpruritic

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Fever, Endocarditis, and Palpable Purpura

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  1. Fever, Endocarditis, and Palpable Purpura NehaOhri MD, University of Colorado Hospital, Robert Janson MD,  VA Eastern Colorado Health Care System

  2. Case • 71M presented with multiple palpable purpura on his LE to his PCP in 1/13. Nonpainful and nonpruritic • Had radiated up his legs to his thighs • A biopsy showed leukocytoclasic vasculitis (LCV). No IF done • He was started on prednisone 10mg PO bid by his PCP which resolved the lesions

  3. Labs 13.2 140 103 25 7.6 178 4.8 27 1.4 14.7 UA w/o bld or protein LDH 286 (<241 is wnl) ANA/ANCA/Hep B/Hep C negative CRP 41.9 mg/L, ESR 67, CH50 <11 CT sinuses – acute maxillary sinusitis CT C/A/P w/o contrast – small b/l renal cysts, moderate mediastinal LAD, no abd LAD 122

  4. PMH: • Gout • BPH • OSA • OA • L TSA • TIA in 2000 • Recurrent sinusitis • Critical mitral stenosis (MVA 1.6 cm2) 2/2 childhood rheumatic fever in eighth grade • pHTN w/RVSP of 72 on TTE 2/2 his MS • Sinusitis treated with antibiotics in 1/13

  5. PMH: • Allergies: allopurinol and moxifloxacin • SH: 1 ppd x 20 years, now quit, social EtOH, no IVDU but used cocaine in the 70s • FH: no FH of CTD. Maternal and paternal side with lung cancer.

  6. Meds: • Clopidogrel 75mg PO daily • Aspirin 81mg PO daily • Prednisone 10mg PO bid • Albuterol/ipratroprium mdi • Simvastatin 40mg PO daily

  7. He continued to take prednisone 10/10 and would the purpura would return every time he tried to wean off • He had a repeat CT thorax w/o contrast in April 2013 which showed slight decrease in mediastinal LAD • In May 2013, he presented to the Denver VA with fatigue, night sweats, 20 lbwt loss, worsening ankle edema and DOE with walking 1 block

  8. Physical Exam • VS: 100.8, 95, 131/76, 96%RA • Talkative, AAOx3 • Anicteric, no oral ulcers, EOMI, PERRL • JVP 12 cm, +HJR • CTAB • Irreg, irreg, II/VI diastolic murmur at the left lateral decubitus position • SNTND • 2+ edema to mid-calf • Palpable purpuric rash over b/l feet to ankles, nontender and nonblanching

  9. What would you order next?

  10. Test results CT C/A/P w/contrast - stable mediastinal LAD, new small R pleural effusion and no other changes from his scans in January 12.5 140 100 9.5 235 68.6%N 4.1 28 1.1 37.5 UA w/o bld or protein 7.1 3.1 LDH 359, Haptoglobin 263 1.1 C3 131, C4 <6, CH50 <12 19 45 Ferritin 275 75 246

  11. Test results • ANA/ANCA/MPO/PR3 negative • RF 1280 • SPEP – elevated alpha ½ • C3 131, C4<6. CH50 <12 • Cryoglobulin negative • APLS triple negative • RHC/LHC: PA 51-55; MV stenosis severe with valve area 0.55 cm2 with gradient 24 mmHg; nonobstructiveCAD • Pearl: A high titer RF and low complements are the “poor man’s cryoglobulin” test and are strongly suspicious for cryoglobulins. Cryoglobulin testing can be falsely negative in the setting of improper handling. This patient’s cryoglobulin test was positive on repeat testing 1 month later.

  12. Micro labs • HIV negative • Hepatitis B and C negative • RPR +, FTAB neg • Blood cultures negative • PPD negative • Bartonellanegative • Brucellanegative

  13. Tests • Q fever (Coxiellaburnetii): • IgG phase I: > 1:128 • IgG phase II: > 1:128 • Coxiellaburnetii serum PCR: positive • Pearl: When cryoglobulinemia, fever, and cardiac valve defects are seen together, think of Q fever

  14. Coxiellaburnetii • Zoonotic gram-negative obligate micro-organism • Common hosts include sheep, cattle and goats • 25-50 cases in the US yearly • 70% of cases in males • Infections can be acute (hepatitis, CNS symptims, PNA) or chronic (endocarditis, cryoglobulinemia, lividoreticularis) • Chronic Q fever more common in patients with a h/o CKD, valvular abnormalities, or immunosuppresion (Walker, Dumler, and Marrie, 2012)

  15. Q fever and cryoglobulinemia • Mixed II cryoglobulinemia is a rare but well described possible sequelae of chronic Q fever • <5% of patients with Q fever endocarditis develop cryoglobulinemia • A case report in 1989 of a woman with concurrent Coxiella endocarditis and cryoglobulinemia was treated with tetracycline qid • Another case report in 2006 used doxycycline and hydroxychloroquinine (HCQ) for life after the patient’s MVR (Rafailidis, Dourakis and Fourlas, 2006) (Torley et al., 1989)

  16. Hospital Course • Doxycycline 100mg bid and HCQ 200mg tidstarted for his chronic Q fever endocarditis/cryoglobulinemia • ID service preferred 2-4 weeks of antibiotics prior to considering MVR • CT surgery would only perform MVR if patient was on 5mg of prednisone or less • Prednisone tapered late May to 5mg bid with some mild exacerbation of his palp purpura

  17. Hospital Course • June 2013 readmitted to hospital with lower GI bleedand worsening purpura on prednisone 5mg bid • Colonoscopy: ulcerated mucosa from cecum to transverse colon • Colon biopsies: c/w ischemic colitis • Cardiac echo: nodular calcifications on mitral valve leaflets with possible vegetation but with severe calcification uncertain

  18. June 2013 Hospital Course • Q fever IgG phase I and II: both 1:2048 • C3 98, C4 <6 • CMV PCR stool positive; serum CMV PCR – detected • Patient was treated with 60mg prednisone and valgancicloviralthough ID didn’t feel the ulcers were related to CMV

  19. How would you treat him? • Dilemma: • Has to have an MVR done for his critical MS causing CHF. This valve is also likely colonized with Coxiella and will cause persistent sequelae . His cryo and CHF will not improve until this is done. • CT surgery won’t do it unless his prednisone is 5mg or lower • His cryoglobulinemia flares when he go below prednisone 20mg • Body cooling during his MVR may be catastrophic if he has active cryoglobulinemia as well

  20. Treatment • Patient was given 2 doses of rituximab 1000mg IV, 2 weeks apart to help wean off prednisone (CD 19 32%) • By the end of June his ESR/CRP were wnl, his prednisone had been tapered to 30mg, and his C3/4 were 91/7 • This is the first case report of cryoglobulinemia due to Q fever that has been treated with rituximab

  21. Hospital Course • The patient had a repeat colonoscopy in July with a few areas of healing ulceration • In August his CD19 was 0%, his C3/4 were 118/24, and his RF was negative. • He had no palpable purpura or lower GI bleeds • 8 weeks post RXN, pt had an uneventful MVR and his mitral valve PCR for Coxiellaburnettiwas positive

  22. Hospital Course • Patient was discharged on 9/23/13 • He was weaned off prednisone in 10/13 • He will be on doxy/HCQ indefinitely • To date, no further episodes of LCV

  23. References: • Enzenauer, R. J., Arend, W. P., & Emlen, J. W. (1991). Mixed cryoglobulinemia associated with chronic Q-fever. The Journal of Rheumatology, 18(1), 76–78. • Rafailidis, P. I., Dourakis, S. P., & Fourlas, C. A. (2006). Q fever endocarditis masquerading as Mixed cryoglobulinemia type II. A case report and review of the literature. BMC Infectious Diseases, 6, 32. doi:10.1186/1471-2334-6-32 • Torley, H., Capell, H., Timbury, M., & McCartney, C. (1989). Chronic Q fever with mixed cryoglobulinaemia. Annals of the Rheumatic Diseases, 48(3), 254–255. • Walker D.H., Dumler J, Marrie T (2012). Chapter 174. Rickettsial Diseases. InLongo D.L., Fauci A.S., Kasper D.L., Hauser S.L., Jameson J, Loscalzo J (Eds),Harrison's Principles of Internal Medicine, 18e. Retrieved January 11, 2014 fromhttp://accesspharmacy.mhmedical.com.hsl-ezproxy.ucdenver.edu/content.aspx?bookid=331&Sectionid=4072692

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